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Cai C, Gu C, Meng C, Wang Y, Wei Q, He S, Lai D, Wang X, Wang T, Qiu Q. DNA hypermethylation of PLTP mediated by DNMT3B aggravates vascular dysfunction in diabetic retinopathy via the AKT/GSK3β signaling pathway. Clin Epigenetics 2025; 17:82. [PMID: 40380281 PMCID: PMC12085079 DOI: 10.1186/s13148-025-01874-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2025] [Accepted: 04/08/2025] [Indexed: 05/19/2025] Open
Abstract
BACKGROUND This study aims to elucidate the effect and mechanism of phospholipid transfer protein (PLTP) on vascular dysfunction in DR and explore the molecular mechanism of abnormal PLTP expression based on DNA methylation. METHODS Human retinal microvascular endothelial cells (HRMECs) cultured in high glucose (HG) and streptozotocin-treated mice were used as DR models to detect and screen the key genes with abnormal promoter DNA methylation. Single-cell sequencing, tube formation and migration assays were employed to verify the relationship between PLTP and vascular function. Additionally, siRNA and luciferase reporter assay were used to study the key enzymes regulating the DNA methylation of PLTP. Transcriptome sequencing, coimmunoprecipitation and GSK3β inhibitor were utilized to identify and validate the key downstream pathways of PLTP. RESULTS DR models exhibited DNA hypermethylation and decreased expression of PLTP. Abnormal PLTP expression was implicated in vascular dysfunction, and PLTP overexpression reversed HG-induced effects on the migration and tube formation of endothelial cells. The siDNMT3B and luciferase reporter assay indicated that DNMT3B is the primary enzyme affecting abnormal methylation. Interestingly, PLTP promoted the phosphorylation of AKT and GSK3β, indicating that PLTP modulates angiogenesis via the AKT/GSK3β signaling pathway. CONCLUSIONS PLTP regulates the proliferation, migration and tube formation of HRMECs, and is involved in maintaining vascular function via the AKT/GSK3β signaling pathway. In HG environment, increased DNMT3B expression upregulates DNA methylation of the PLTP promoter, downregulating PLTP expression and leading to vascular dysfunction in DR.
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Affiliation(s)
- Chunyang Cai
- Department of Ophthalmology, Tong Ren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
- National Clinical Research Center for Eye Diseases; Shanghai Key Laboratory of Ocular Fundus Diseases; Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, People's Republic of China
| | - Chufeng Gu
- Department of Ophthalmology, Fuzhou University Affiliated Provincial Hospital, Shengli Clinical College of Fujian Medical University, Fuzhou, Fujian, People's Republic of China.
| | - Chunren Meng
- Department of Ophthalmology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People's Republic of China
| | - Yujie Wang
- Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Australia
| | - Qingquan Wei
- Department of Ophthalmology, Tong Ren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
- High Altitude Ocular Disease Research Center of People's Hospital of Shigatse City and Tongren Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
| | - Shuai He
- Department of Ophthalmology, Tong Ren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
| | - Dongwei Lai
- Department of Ophthalmology, Tong Ren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
- National Clinical Research Center for Eye Diseases; Shanghai Key Laboratory of Ocular Fundus Diseases; Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, People's Republic of China
| | - Xingyun Wang
- Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
| | - Tengfei Wang
- Department of Ophthalmology, Tong Ren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
- Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
| | - Qinghua Qiu
- Department of Ophthalmology, Tong Ren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
- Department of Ophthalmology, Shigatse People's Hospital, Shigatse, Tibet, People's Republic of China.
- High Altitude Ocular Disease Research Center of People's Hospital of Shigatse City and Tongren Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
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Zhang H, Li Y, Xu Q, Fang Z. Unveiling the molecular mechanisms of stigmasterol on diabetic retinopathy: BNM framework construction and experimental validation. Front Med (Lausanne) 2025; 12:1537139. [PMID: 40417668 PMCID: PMC12098638 DOI: 10.3389/fmed.2025.1537139] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2024] [Accepted: 04/23/2025] [Indexed: 05/27/2025] Open
Abstract
Background Diabetic retinopathy (DR), one of the most common complications of diabetes, severely impacts patients' quality of life. The combined use of the traditional Chinese medicines Astragalus, Fructus ligustris, and Cornus officinalis has yielded considerable therapeutic effects in clinical DR treatment. Methods In this study, a multimodule framework (BNM) encompassing bioinformatics, network pharmacology, and machine learning (ML) based on molecular fingerprints was innovatively developed to thoroughly investigate the molecular mechanisms of this Chinese medicine in treating DR. Results A total of 40 active components and 12 core targets were identified. Enrichment analysis identified key pathways such as VEGF signaling pathway, TNF signaling pathway and HIF-1 signaling pathway. Prediction models using key targets, such as PPARG, were constructed from the GEO database and validated via immune infiltration analysis and molecular docking, revealing that PPARG may be a potential target for DR treatment. Moreover, the core component of this Chinese medicine, stigmasterol, was identified using a ML model based on molecular fingerprints. In vivo experiments demonstrated that stigmasterol can regulate glucose and lipid metabolism, improve systemic inflammatory levels, and ameliorate ocular vascular changes in DR by modulating the expression of PPARG. Conclusion The BNM framework suggests that PPARG may be an important target for stigmasterol in the treatment of DR, with its mechanism potentially related to the VEGF/VEGFR pathway.
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Affiliation(s)
| | | | | | - Zhaohui Fang
- Anhui University of Chinese Medicine, Hefei, China
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Lu S, Li H, Ma C, Li X. Analysis of risk factors for vitreous hemorrhage and recurrent hemorrhage after vitrectomy in patients with diabetic retinopathy. BMC Ophthalmol 2025; 25:274. [PMID: 40335915 PMCID: PMC12057211 DOI: 10.1186/s12886-025-04112-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2025] [Accepted: 04/29/2025] [Indexed: 05/09/2025] Open
Abstract
PURPOSE To investigate the risk factors associated with recurrent hemorrhage following vitrectomy surgical intervention for diabetic retinopathy (DR). METHODS A retrospective analysis was conducted on 579 eyes diagnosed with DR necessitating surgical intervention. These cases were categorized into two groups: recurrent hemorrhage and non-recurrent hemorrhage. Comparative, random forest (RF), and regression analyses were subsequently performed to evaluate variables pertaining to patients' demographic information, clinical examination and blood test results, treatment approaches, lifestyle habits, and overall health status. RESULTS This study compared patients with recurrent and non-recurrent hemorrhages, revealing significant differences in factors such as endodiathermy, anticoagulant use, cerebrovascular diseases, smoking status, glycosylated hemoglobin levels and BMI. Patients with no recurrent hemorrhage have faster vision recovery. The univariable logistic regression analysis indicated that cerebrovascular disease (OR = 7.87, P < 0.001), anticoagulant use (OR = 16.72, P < 0.001), and elevated glycated hemoglobin levels (OR = 21.22, P < 0.001) exhibited strong associations with recurrent hemorrhage. The multivariable logistic regression analysis indicated that recurrent hemorrhage risk factors include anticoagulant use (OR = 120.77, P = 0.020) and glycated hemoglobin levels (OR = 18.41, P = 0.001). CONCLUSIONS Recurrent postoperative hemorrhage is influenced by several factors, notably the use of intraoperative endodiathermy, adjustments in ocular therapy, and management of the patient's systemic condition. In clinical practice, careful consideration of these factors is essential to mitigate postoperative hemorrhage in patients.
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Affiliation(s)
- Shuwen Lu
- Department of Ophthalmology, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan, China.
- Department of Ophthalmology, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, No. 19 Renmin Road, Zhengzhou, 450000, Henan, China.
| | - Haoyu Li
- Department of Ophthalmology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Chao Ma
- Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Xian Li
- Manchester Royal Eye Hospital, Manchester University NHS Foundation Trust, Manchester, UK
- Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK
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Grajales-Garcia1 DP. [Comment on the article "Retinal ischemia as an early marker of renal failure in non-proliferative retinopathy"]. REVISTA MEDICA DEL INSTITUTO MEXICANO DEL SEGURO SOCIAL 2025; 63:e6151. [PMID: 40333002 PMCID: PMC12119117 DOI: 10.5281/zenodo.15178487] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 05/08/2025]
Abstract
Regarding the article "Retinal ischemia as an early marker of renal failure in non-proliferative retinopathy" by Muñoz-Cornejo et al., retinal ischemia reflects microvascular damage, hyperglycemia causes endothelial damage, vascular occlusion, and the release of proangiogenic factors, which is linked with the presence of retinopathy and nephropathy. However, the study has limitations: it uses outdated terminology, it does not evaluate key renal markers, and it does not control for confounding factors. Although 25 (45%) of the patients with retinal ischemia had albuminuria, no correlation with renal deterioration was proven, and renal damage could precede ocular damage. More precise parameters are needed to establish this association.
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Affiliation(s)
- Dulce Paola Grajales-Garcia1
- Instituto Mexicano del Seguro Social, Hospital General Regional No. 1 “Dr. Carlos MacGregor Sánchez Navarro”, Servicio de Nefrología. Ciudad de México, MéxicoInstituto Mexicano del Seguro SocialMéxico
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Kasem E, Watfa M, Afif A, Hasan R, Mansour M, Almhmoud H, Zaino B. Optogenetic therapy for retinal degenerative diseases: A review. Eur J Ophthalmol 2025:11206721251335560. [PMID: 40255074 DOI: 10.1177/11206721251335560] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/22/2025]
Abstract
Optogenetics, a cutting-edge tool in novel gene manipulation and drug discovery, holds significant therapeutic potential for a variety of neurological disorders, including retinal diseases. Retinal diseases such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP), significantly impair quality of life and cause severe visual impairment due to limited treatment options and a general lack of awareness. The increasing incidence of these degenerative conditions underscores the need for innovative solutions, such as optogenetics. Optogenetic therapy introduces genes coding for light-sensitive proteins, which are controlled by light signals to make neurons photosensitive. This precise targeting approach does not require specific gene intervention and can bypass dysfunctional photoreceptors, offering a treatment option for various degenerative and dystrophic eye diseases. Successful outcomes in patients with late-stage genetic retinal diseases and numerous clinical trials suggest that optogenetics could be an effective treatment for humans. This review provides an overview of the current landscape of optogenetic therapy, discusses its challenges, and summarizes the findings of ongoing clinical trials for neural and visual restoration.
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Affiliation(s)
- Ehab Kasem
- Department of Plastic and Reconstructive Surgery, Damascus University, Almwasat Hospital, Damascus, Syria
| | - Masa Watfa
- Department of Hematology and Blood Transfusion, Tishreen University Hospital, Lattakia, Syria
| | - Ali Afif
- Faculty of Medicine, Tishreen University, Latakia, Syria
| | - Raghad Hasan
- Faculty of Medicine, Tishreen University, Latakia, Syria
| | - Majd Mansour
- Faculty of Medicine, Tishreen University, Latakia, Syria
| | - Haya Almhmoud
- Faculty of Medicine, Tishreen University, Latakia, Syria
| | - Basem Zaino
- Department of Pathology, Tishreen University Hospital, Lattakia, Syria
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Nowak I, Kubina R, Strzałka-Mrozik B. Therapeutic Potential of Hexahydrocurcumin in the Regeneration and Protection of the Retinal Pigment Epithelium. Pharmaceuticals (Basel) 2025; 18:554. [PMID: 40283989 PMCID: PMC12030554 DOI: 10.3390/ph18040554] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2025] [Revised: 04/02/2025] [Accepted: 04/07/2025] [Indexed: 04/29/2025] Open
Abstract
Hexahydrocurcumin (HHC), the primary metabolite of curcumin, shows promising therapeutic potential due to its antioxidant and anti-inflammatory properties. The retinal pigment epithelium (RPE) plays a crucial role in maintaining retinal homeostasis; however, its dysfunction-linked to oxidative stress and chronic inflammation-contributes to the progression of degenerative diseases such as age-related macular degeneration (AMD). This review highlights the therapeutic potential of HHC in protecting and regenerating RPE cells. It explores the effects of oxidative stress on the RPE, the mechanisms underlying its damage, and the involvement of reactive oxygen species (ROS) and inflammatory mediators. HHC has demonstrated the ability to modulate these pathways by activating nuclear factor erythroid 2-related factor 2 (NRF2), enhancing antioxidant defenses, and inhibiting pro-inflammatory cytokine production. Preclinical studies suggest that HHC mitigates vascular remodeling and endothelial dysfunction by reducing the expression of transforming growth factor β (TGF-β1) and matrix metalloproteinase-9 (MMP-9). Moreover, HHC improves nitric oxide bioavailability and promotes nitric oxide synthase expression, thereby counteracting oxidative stress-induced vascular damage. Emerging evidence indicates that HHC may be a promising candidate for the treatment of retinal degenerative diseases, particularly those associated with oxidative stress and inflammation. However, further studies, including clinical trials, are essential to confirm its efficacy and elucidate the precise mechanisms underlying HHC's protective effects on RPE cells.
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Affiliation(s)
- Ilona Nowak
- Department of Molecular Biology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 41-200 Sosnowiec, Poland;
- Silesia LabMed: Centre for Research and Implementation, Medical University of Silesia, 41-752 Katowice, Poland;
| | - Robert Kubina
- Silesia LabMed: Centre for Research and Implementation, Medical University of Silesia, 41-752 Katowice, Poland;
- Department of Pathology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 41-200 Sosnowiec, Poland
| | - Barbara Strzałka-Mrozik
- Department of Molecular Biology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 41-200 Sosnowiec, Poland;
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Böhm EW, Buonfiglio F, Korb CA, Dauth A, Pfeiffer N, Bręborowicz A, Gericke A. Potential of Sulodexide in the Treatment of Diabetic Retinopathy and Retinal Vein Occlusion. Thromb Haemost 2025; 125:291-307. [PMID: 39293483 DOI: 10.1055/s-0044-1791232] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/20/2024]
Abstract
Retinal vascular diseases, such as diabetic retinopathy or retinal vein occlusion, are common causes of severe vision loss. Central to the pathophysiology of these conditions are endothelial dysfunction, inflammation, capillary leakage, ischemia, and pathological neoangiogenesis. Capillary damage leads to leakage and the development of macular edema, which is associated with vision loss and requires complex treatment. Sulodexide, a glycosaminoglycan composed of heparan sulfate and dermatan sulfate with high oral bioavailability, exhibits several favorable pharmacologic properties, including antithrombotic, anti-inflammatory, and endothelium-protective effects. Additionally, treatment with sulodexide has been associated with the reduction of oxidative stress and decreased expression of angiogenic growth factors, such as vascular endothelial growth factor. This review aims to provide an overview of the pharmacological properties, mechanisms of action, and therapeutic effects of sulodexide. Furthermore, its potential for clinical application in venous and diabetic diseases, such as venous thromboembolism, chronic venous insufficiency, peripheral artery disease, or diabetic nephropathy, is summarized. We also present experimental and clinical studies evaluating the potential of sulodexide in ocular conditions and discuss its therapeutic implications for the treatment of retinal vascular diseases.
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Affiliation(s)
- Elsa Wilma Böhm
- Department of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany
| | - Francesco Buonfiglio
- Department of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany
| | - Christina A Korb
- Department of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany
| | - Alice Dauth
- Department of Neurosurgery, University Medical Center Mainz, Johannes Gutenberg University of Mainz, Mainz, Germany
| | - Norbert Pfeiffer
- Department of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany
| | - Andrzej Bręborowicz
- Department of Pathophysiology, Poznan University of Medical Sciences, Poznan, Poland
- Collegium Medicum, Zielona Góra University, Zielona Góra, Poland
| | - Adrian Gericke
- Department of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany
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Sun W, Wang R, Gong K, Wang L, Li F, Deng J. Paeoniflorin-mediated downregulation of VEGFA: unveiling the therapeutic mechanism of buyang huanwu decoction in diabetic retinopathy. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025; 398:4571-4582. [PMID: 39508875 DOI: 10.1007/s00210-024-03562-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Accepted: 10/22/2024] [Indexed: 11/15/2024]
Abstract
Diabetic retinopathy (DR) is a leading cause of blindness globally. Buyang Huanwu decoction (BHD) is a traditional Chinese medicine for treating DR, but its therapeutic mechanisms are not fully understood. This study aimed to elucidate and validate the underlying mechanisms of BHD in DR treatment through network pharmacology and in vitro experiments. We identified active compounds in BHD and their associated targets using the TCMSP and SwissTargetPrediction. DR-related targets were sourced from GeneCards, NCBI, and OMIM databases. The protein-protein interaction (PPI) network and enrichment analyses were employed to predict common targets and pathways. Subsequent molecular docking and in vitro experiments, including cell viability assays, RT-qPCR, flow cytometry, and Western blot, were conducted to validate the anti-DR mechanism of BHD. Network pharmacology identified paeoniflorin as a key active compound in BHD for treating DR, with VEGFA emerging as a central target. Molecular docking suggested a strong binding affinity between paeoniflorin and VEGFA. In vitro experiments confirmed that paeoniflorin attenuated high glucose-induced increases in cell viability, migration, apoptosis, and inflammatory cytokine expression in retinal pigment epithelial cells. The therapeutic effect of paeoniflorin was primarily mediated through the downregulation of VEGFA expression. Our study demonstrates that paeoniflorin, a key active compound in BHD, effectively mitigates DR by downregulating VEGFA expression and reducing high glucose-induced cellular alterations, thereby highlighting its potential as a therapeutic agent for DR.
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Affiliation(s)
- Wentao Sun
- Shaanxi Eye Hospital, Xi'an People's Hospital (Xi'an Fourth Hospital), Affiliated People's Hospital of Northwest University, 21 Jiefang Road, Xi'an, 710004, China
| | - Rui Wang
- Tongchuan Wuguan Hospital, Tongchuan, 712100, China
| | - Ke Gong
- Shaanxi Eye Hospital, Xi'an People's Hospital (Xi'an Fourth Hospital), Affiliated People's Hospital of Northwest University, 21 Jiefang Road, Xi'an, 710004, China
| | - Liping Wang
- Shaanxi Eye Hospital, Xi'an People's Hospital (Xi'an Fourth Hospital), Affiliated People's Hospital of Northwest University, 21 Jiefang Road, Xi'an, 710004, China
| | - Fengzhi Li
- Shaanxi Eye Hospital, Xi'an People's Hospital (Xi'an Fourth Hospital), Affiliated People's Hospital of Northwest University, 21 Jiefang Road, Xi'an, 710004, China
| | - Jin Deng
- Shaanxi Eye Hospital, Xi'an People's Hospital (Xi'an Fourth Hospital), Affiliated People's Hospital of Northwest University, 21 Jiefang Road, Xi'an, 710004, China.
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Go MY, Kim J, Jeon CY, Kim M, Shin DW. Pinitol Improves Lipopolysaccharide-Induced Cellular Damage in Human Dermal Microvascular Endothelial Cells. Molecules 2025; 30:1513. [PMID: 40286119 PMCID: PMC11990420 DOI: 10.3390/molecules30071513] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2024] [Revised: 03/20/2025] [Accepted: 03/26/2025] [Indexed: 04/29/2025] Open
Abstract
3-O-Methyl-D-chiro-inositol (pinitol) has been reported to possess insulin-like effects and is known as one of the anti-diabetic agents for improving muscle and liver function. However, the beneficial effects of pinitol on human dermal microvascular endothelial cells (HDMECs) are not well understood. In this study, we investigated whether pinitol could protect HDMECs from damage induced by lipopolysaccharides (LPSs), which cause various cell defects. We observed that pinitol enhanced wound healing for LPS-damaged HDMECs. We found that pinitol significantly downregulated the LPS-induced upregulation of reactive oxygen species (ROS). Pinitol also significantly restored the mitochondrial membrane potential in these cells. Immunofluorescence analysis revealed that pinitol notably reduced the nuclear localization of NF-κB in LPS-damaged HDMECs. Furthermore, we demonstrated that pinitol decreased the phosphorylation levels of the MAPK family in LPS-damaged HDMECs. Interestingly, we observed that pinitol improved tube formation in LPS-damaged HDMECs. Taken together, we suggest that pinitol exerts several beneficial effects on LPS-damaged HDMECs and may be a promising therapeutic agent for improving vascular-related skin diseases.
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Affiliation(s)
| | | | | | | | - Dong Wook Shin
- Research Institute for Biomedical and Health Science, Konkuk University, Chungju 27478, Republic of Korea; (M.Y.G.); (J.K.); (C.Y.J.); (M.K.)
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Shumye AF, Tegegne MM, Bekele MM, Woredekal AT, Eticha BL. Burden of diabetic macular oedema and its associated factors among adult patients with diabetes attending comprehensive specialised hospitals in Northwest Ethiopia, 2023: a multicentre cross-sectional study. BMJ Open 2025; 15:e088507. [PMID: 40090690 PMCID: PMC11911699 DOI: 10.1136/bmjopen-2024-088507] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Accepted: 02/28/2025] [Indexed: 03/18/2025] Open
Abstract
OBJECTIVE This study aimed to assess the prevalence of diabetic macular oedema and its associated factors among adult patients with diabetes attending comprehensive specialised hospitals in Northwest Ethiopia in 2023. DESIGN An institution-based, cross-sectional study. SETTING The study was conducted at the University of Gondar, Felege Hiwot and Debre Markos comprehensive specialised hospitals in Northwest Ethiopia from 8 May to 15 June 2023. PARTICIPANTS This study was conducted on 890 adult patients with diabetes selected using a systematic random sampling technique. OUTCOME MEASURES Participants with diabetic macular oedema were assessed using slit lamp biomicroscopy with a +90 dioptre Volk lens. Blood glucose levels were measured by fasting blood sugar tests. Data were collected through physical examination, review of medical records and face-to-face interview. RESULTS Among a total of 890 study participants, the prevalence of diabetic macular oedema was 25.8% (95% CI 23.1 to 28.8). Peripheral neuropathy (adjusted OR (AOR)=3.02, 95% CI 1.76 to 5.29), hypertension (AOR=1.98, 95% CI 1.24 to 3.17), poor blood glucose control (AOR=5.06, 95% CI 2.95 to 8.67), obesity (AOR=5.03, 95% CI 2.50 to 10.13), longer duration of diabetes mellitus (AOR=3.78, 95% CI 2.21 to 6.24) and poor adherence to diabetic medication (AOR=2.06, 95% CI 1.32 to 3.28) were significantly associated with diabetic macular oedema. CONCLUSION In Northwest Ethiopia, a quarter of patients with diabetes were found to have diabetic macular oedema. Factors such as peripheral neuropathy, hypertension, poor blood glucose levels, obesity, long duration of diabetes mellitus and poor adherence to diabetic medications were significantly associated with diabetic macular oedema. Improvement of glucose control and exercise for optimal body weight maintenance are recommended to prevent the development of diabetic macular oedema.
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Affiliation(s)
- Abebech Fikade Shumye
- Department of Optometry, College of Medicine and Health Sciences, Comprehensive Specialized Hospital, University of Gondar, Gondar, Ethiopia
| | - Mebratu Mulusew Tegegne
- Department of Optometry, College of Medicine and Health Sciences, Comprehensive Specialized Hospital, University of Gondar, Gondar, Ethiopia
| | - Matiyas Mamo Bekele
- Department of Optometry, College of Medicine and Health Sciences, Comprehensive Specialized Hospital, University of Gondar, Gondar, Ethiopia
| | - Asamere Tsegaw Woredekal
- Department of Ophthalmology, University of Gondar College of Medicine and Health Sciences, Gondar, Ethiopia
| | - Biruk Lelisa Eticha
- Department of Optometry, College of Medicine and Health Sciences, Comprehensive Specialized Hospital, University of Gondar, Gondar, Ethiopia
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Wang N, Li H, Sun Q, Han X, Su S. The Exploration of Disturbance of Capillary and Photoreceptor Communication Networks in Diabetic Retinopathy Through Single-Cell RNA-Seq. J Cell Mol Med 2025; 29:e70442. [PMID: 40032635 PMCID: PMC11875770 DOI: 10.1111/jcmm.70442] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2024] [Revised: 01/24/2025] [Accepted: 02/12/2025] [Indexed: 03/05/2025] Open
Abstract
This study investigates the differences in ligand-receptor interactions between the communication network of vascular endothelial cells (ECs) and photoreceptor cells (PRCs)in diabetic retinopathy (DR) the mechanism was verified by animal experiments. The GSE209872 data set, including retinal specimens from five Sprague-Dawley rats induced by streptozotocin, was obtained from Gene Expression Omnibus. CM and EC data were extracted individually for reclustering, functional enrichment and trajectory analyses. Cell communication analysis was conducted to investigate the altered signals and significant ligand-receptor interactions. Moreover, novel ligand-receptor interactions were validated using immunofluorescence staining using 2, 4 and 8 weeks DR model; DR was treated with AAV-shANGPTL4, and retinal function was detected by Haematoxylin and eosin staining (HE), TUNEL and ELISA. The expression of ligand-receptor in DR Retina was detected by qPCR and immunohistochemistry. Nine cell types were determined in DR. Cellular communication results revealed four signalling pathways, including PTN, MK, ANGPTL and CXCL, that were significantly changed in DR. Furthermore, 3 ligand-receptor pairs (Ptn-Ncl, Mkd-Ncl and Angptl4-Sdc4) were obviously upregulated between ECs and PRCs, the expression of which was verified via immunofluorescence in the DR model. After treatment with AAV-shANGPTL4, the retinal thickness and average density of RGCs were decreased (p < 0.05). TUNEL staining showed that knocking down ANGPTL4 reduced the apoptosis of DR (p < 0.05), and VEGF and IGF-1 expression were downregulated (p < 0.01). The expression of ligand-receptors also decreased in the DR Model (p < 0.01). The vascular ECs and PRCs demonstrate significant heterogeneities in DR. ANGPTL4 was a decreased ligand-receptor expression and improved retinal function as a potential therapeutic target against DR.
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Affiliation(s)
- Ning Wang
- Eye Hospital, The First Affiliated HospitalHarbin Medical UniversityHarbinHeilongjiangChina
| | - Huibo Li
- Department of Hematology, The First Affiliated HospitalHarbin Medical UniversityHarbinHeilongjiangChina
| | - Qinqin Sun
- Eye Hospital, The First Affiliated HospitalHarbin Medical UniversityHarbinHeilongjiangChina
| | - Xuelian Han
- Eye Hospital, The First Affiliated HospitalHarbin Medical UniversityHarbinHeilongjiangChina
| | - Sheng Su
- Eye Hospital, The First Affiliated HospitalHarbin Medical UniversityHarbinHeilongjiangChina
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Wang Y, Song SY, Song Y, Wang Y, Wan ZW, Sun P, Yu XM, Deng B, Zeng KH. Resveratrol Protects Müller Cells Against Ferroptosis in the Early Stage of Diabetic Retinopathy by Regulating the Nrf2/GPx4/PTGS2 Pathway. Mol Neurobiol 2025; 62:3412-3427. [PMID: 39292340 DOI: 10.1007/s12035-024-04496-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2024] [Accepted: 09/12/2024] [Indexed: 09/19/2024]
Abstract
The aim of this study was to investigate the anti-ferroptotic effect of resveratrol (RSV) on retinal Müller cells (RMCs) in the early stages of diabetic retinopathy (DR) via the nuclear factor erythroid 2-related factor 2 (Nrf2)/glutathione peroxidase 4 (GPx4)/prostaglandin-endoperoxide synthase 2 (PTGS2). The retina was obtained from normal and diabetic Sprague-Dawley rats or wild-type and Nrf2 knockout (KO) diabetic mice, with or without RSV (10 mg/kg/d) treatment for 12 weeks. RMCs transfected with or without SiNrf2 were cultured with high glucose and RSV (20 mM). The retinal neurofunctional changes were measured by electroretinogram (ERG). The retinal inner nuclear layer cell mitochondrial morphological changes were detected by transmission electron microscopy. The cell viabilities were measured by cell counting kit-8 (CCK-8) assay. The levels of Fe2+, malonic dialdehyde (MDA), and glutathione (GSH) were measured by colorimetric method. The expression of Nrf2, GPx4, and PTGS2 was detected by quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, and immunocytochemistry. In vivo, RSV inhibited retinal neurofunctional changes and mitochondrial morphological changes; decreased Fe2+, MDA, and PTGS2; and increased GSH, Nrf2, and GPx4 in retina of DM rats. In vitro, RSV decreased MDA and PTGS2 and increased cell viability, GSH, Nrf2, and GPx4. In vivo and vitro, the role of Nrf2-regulated signaling pathway in anti-ferroptosis by RSV was further confirmed using Nrf2 KO mice and pre-transfected SiNrf2 in RMCs. These findings indicated that RSV is a potential therapeutic option for DR and that Nrf2/GPx4/PTGS2 plays a role in the anti-ferroptosis mechanism of RSV on RMCs.
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Affiliation(s)
- Yi Wang
- Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Si-Yuan Song
- Baylor College of Medicine, Houston, TX, 77030, USA
| | - Yi Song
- Department of Clinical Nutrition, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610054, China
| | - Yuan Wang
- Department of Clinical Nutrition, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610054, China
| | - Zheng-Wei Wan
- Institute of Health Management & Department of Health Management Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610054, China
| | - Ping Sun
- Institute of Health Management & Department of Health Management Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610054, China
| | - Xue-Mei Yu
- Department of Clinical Nutrition, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610054, China
| | - Bo Deng
- Department of Clinical Nutrition, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610054, China.
| | - Kai-Hong Zeng
- Institute of Health Management & Department of Health Management Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610054, China.
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D'Angelo A, Lixi F, Vitiello L, Gagliardi V, Pellegrino A, Giannaccare G. The Role of Diet and Oral Supplementation for the Management of Diabetic Retinopathy and Diabetic Macular Edema: A Narrative Review. BIOMED RESEARCH INTERNATIONAL 2025; 2025:6654976. [PMID: 40041571 PMCID: PMC11876532 DOI: 10.1155/bmri/6654976] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/29/2024] [Accepted: 02/08/2025] [Indexed: 03/06/2025]
Abstract
Globally, diabetic retinopathy (DR) and diabetic macular edema (DME) are the leading causes of visual loss in working people. Current treatment approaches mostly target proliferative DR and DME, such as intravitreal injections of antivascular endothelial growth factor agents and laser photocoagulation. Before DR progresses into the more severe, sight-threatening proliferative stage, patients with early stages of the disease must get early and appropriate care. It has been suggested that nutraceuticals, which are natural functional foods with minimal adverse effects, may help diabetic patients with DR and DME. Several in vitro and in vivo studies were carried out over the last years, showing the potential benefits of several nutraceuticals in DR due to their neuroprotective, vasoprotective, anti-inflammatory, and antioxidant properties. Although most of the research is restricted to animal models and many nutraceuticals have low bioavailability, these compounds may adjuvate and implement conventional DR therapies. The purpose of this review is (i) to summarize the complex pathophysiology underlying DR and DME and (ii) to examine the main natural-derived molecules and dietary habits that can assist conventional therapies for the clinical management of DR and DME.
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Affiliation(s)
- Angela D'Angelo
- Department of Clinical Sciences and Community Health–Department of Excellence 2023–2027, University of Milan, Milan, Italy
| | - Filippo Lixi
- Department of Surgical Sciences, Eye Clinic, University of Cagliari, Cagliari, Italy
| | - Livio Vitiello
- Department of Head and Neck, Eye Unit, “Luigi Curto” Hospital-Azienda Sanitaria Locale Salerno, Polla, Italy
| | - Vincenzo Gagliardi
- Department of Head and Neck, Eye Unit, “Luigi Curto” Hospital-Azienda Sanitaria Locale Salerno, Polla, Italy
| | - Alfonso Pellegrino
- Department of Head and Neck, Eye Unit, “Luigi Curto” Hospital-Azienda Sanitaria Locale Salerno, Polla, Italy
| | - Giuseppe Giannaccare
- Department of Surgical Sciences, Eye Clinic, University of Cagliari, Cagliari, Italy
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Torres-Isidro O, González-Montoya M, Vargas-Vargas MA, Florian-Rodriguez U, García-Berumen CI, Montoya-Pérez R, Saavedra-Molina A, Calderón-Cortés E, Rodríguez-Orozco AR, Cortés-Rojo C. Anti-Aging Potential of Avocado Oil via Its Antioxidant Effects. Pharmaceuticals (Basel) 2025; 18:246. [PMID: 40006059 PMCID: PMC11858862 DOI: 10.3390/ph18020246] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2025] [Revised: 02/06/2025] [Accepted: 02/06/2025] [Indexed: 02/27/2025] Open
Abstract
Aging is a process characterized by tissue degeneration, increased susceptibility to chronic degenerative diseases, infections, and the appearance of neoplasms, which leads to disability and a reduction in the length and quality of life. This phenomenon is the result of the convergence of multiple processes, including mitochondrial dysfunction, fibrosis, inflammation, dysregulation of cell death processes, and immunosenescence. These processes have as their point of convergence an increase in the production of ROS. Avocado oil (Persea americana Mill.) contains a diverse array of bioactive compounds, including oleic acid, phytosterols, chlorophylls, xanthones, xanthines, and carotenoids. These bioactive compounds have the capacity to modulate the excessive production of ROS, thereby reducing the progression of age-related diseases and extending lifespan in experimental models of aging. In addition, several studies have demonstrated the efficacy of avocado oil in mitigating age-related diseases, including hypertension; insulin resistance; diabetes; non-alcoholic liver disease; and degenerative processes such as hearing loss, cognitive decline, neurodegeneration, and impaired wound healing. In light of these findings, it is hypothesized that avocado oil is a promising agent capable of promoting healthspan in later stages of life owing to its direct antioxidant actions and the activation of pathways that enhance endogenous antioxidant levels.
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Affiliation(s)
- Olin Torres-Isidro
- Instituto de Investigaciones Químico-Biológicas, Universidad Michoacana de San Nicolás de Hidalgo, Morelia 58030, Michoacán, Mexico; (O.T.-I.); (M.G.-M.); (M.A.V.-V.); (C.I.G.-B.); (R.M.-P.); (A.S.-M.)
| | - Marcela González-Montoya
- Instituto de Investigaciones Químico-Biológicas, Universidad Michoacana de San Nicolás de Hidalgo, Morelia 58030, Michoacán, Mexico; (O.T.-I.); (M.G.-M.); (M.A.V.-V.); (C.I.G.-B.); (R.M.-P.); (A.S.-M.)
| | - Manuel Alejandro Vargas-Vargas
- Instituto de Investigaciones Químico-Biológicas, Universidad Michoacana de San Nicolás de Hidalgo, Morelia 58030, Michoacán, Mexico; (O.T.-I.); (M.G.-M.); (M.A.V.-V.); (C.I.G.-B.); (R.M.-P.); (A.S.-M.)
| | - Ulises Florian-Rodriguez
- Facultad de Químico Farmacobiología, Universidad Michoacana de San Nicolás de Hidalgo, Morelia 58240, Michoacán, Mexico;
| | - Claudia Isabel García-Berumen
- Instituto de Investigaciones Químico-Biológicas, Universidad Michoacana de San Nicolás de Hidalgo, Morelia 58030, Michoacán, Mexico; (O.T.-I.); (M.G.-M.); (M.A.V.-V.); (C.I.G.-B.); (R.M.-P.); (A.S.-M.)
| | - Rocío Montoya-Pérez
- Instituto de Investigaciones Químico-Biológicas, Universidad Michoacana de San Nicolás de Hidalgo, Morelia 58030, Michoacán, Mexico; (O.T.-I.); (M.G.-M.); (M.A.V.-V.); (C.I.G.-B.); (R.M.-P.); (A.S.-M.)
| | - Alfredo Saavedra-Molina
- Instituto de Investigaciones Químico-Biológicas, Universidad Michoacana de San Nicolás de Hidalgo, Morelia 58030, Michoacán, Mexico; (O.T.-I.); (M.G.-M.); (M.A.V.-V.); (C.I.G.-B.); (R.M.-P.); (A.S.-M.)
| | - Elizabeth Calderón-Cortés
- Facultad de Enfermería, Universidad Michoacana de San Nicolás de Hidalgo, Morelia 58260, Michoacán, Mexico;
| | - Alain Raimundo Rodríguez-Orozco
- Facultad de Ciencias Médicas y Biológicas “Dr. Ignacio Chávez”, Universidad Michoacana de San Nicolás de Hidalgo, Morelia 58020, Michoacán, Mexico;
| | - Christian Cortés-Rojo
- Instituto de Investigaciones Químico-Biológicas, Universidad Michoacana de San Nicolás de Hidalgo, Morelia 58030, Michoacán, Mexico; (O.T.-I.); (M.G.-M.); (M.A.V.-V.); (C.I.G.-B.); (R.M.-P.); (A.S.-M.)
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Chen N, Zhu Z, Gong D, Xu X, Hu X, Yang W. Comparative analysis of retinal vascular structural parameters in populations with different glucose metabolism status based on color fundus photography and artificial intelligence. Front Cell Dev Biol 2025; 13:1550176. [PMID: 39963156 PMCID: PMC11830720 DOI: 10.3389/fcell.2025.1550176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2024] [Accepted: 01/15/2025] [Indexed: 02/20/2025] Open
Abstract
Objective Measure and analyze retinal vascular parameters in individuals with varying glucose metabolism, explore preclinical retinal microstructure changes related to diabetic retinopathy (DR), and assess glucose metabolism's impact on retinal structure. Methods The study employed a cross-sectional design encompassing a 4-year period from 2020 to 2024. Fundus photographs from 320 individuals (2020-2024) were categorized into non-diabetes, pre-diabetes, type 2 diabetes mellitus (T2DM) without DR, and T2DM with mild-to-moderate non-proliferative DR (NPDR) groups. An artificial intelligence (AI)-based automatic measurement system was used to quantify retinal blood vessels in the fundus color photographic images, enabling inter-group parameter comparison and analysis of significant differences. Results Between January 2020 and June 2024, fundus color photographs were collected from 320 individuals and categorized into four groups: non-diabetes (n = 54), pre-diabetes (n = 71), T2DM without overt DR (n = 144), and T2DM with mild-to-moderate NPDR (n = 51). In pairwise comparisons among individuals with pre-diabetes, T2DM without DR, and T2DM with mild-to-moderate NPDR. Fasting blood glucose (FBG), glycated hemoglobin (HbA1c), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were significantly different (P < 0.05). Within the T2DM population, FBG, HbA1c, age, SBP, and DBP were significant predictors for mild-to-moderate NPDR (P < 0.05). Average venous branching number (branch_avg_v) was significantly different among pre-diabetes, T2DM without DR, and T2DM with mild-to-moderate NPDR groups. In patients with T2DM with mild-to-moderate NPDR, Average length of arteries (length_avg_a) and average length of veins (length_avg_v) increased, whereas branch_avg_v, average venous branching angle (angle_avg_v), average venous branching asymmetry (asymmetry_avg_v),overall length density (vessel_length_density), and vessel area density (vessel_density) decreased significantly (P < 0.05). Logistic regression analysis identified length_avg_a, branch_avg_v, angle_avg_v, asymmetry_avg_v, vessel_length_density, and vessel_density as independent predictors of mild-to-moderate NPDR in patients with T2DM. Receiver Operating Characteristic (ROC) curve analysis demonstrated that length_avg_a, length_avg_v, branch_avg_v, angle_avg_v, asymmetry_avg_v, vessel_length_density, and vessel_density had diagnostic value for mild-to-moderate NPDR (P < 0.05). Conclusion In individuals diagnosed with T2DM, specific retinal vascular parameters, such as branch_avg_v and vessel_density, demonstrate a significant correlation with mild-to-moderate NPDR. These parameters hold promise as preclinical biomarkers for detecting vascular abnormalities associated with DR.
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Affiliation(s)
- Naimei Chen
- Department of Ophthalmology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
- Department of Ophthalmology, Huaian Hospital of Huaian City, Huaian, China
| | - Zhentao Zhu
- Department of Ophthalmology, Huaian Hospital of Huaian City, Huaian, China
| | - Di Gong
- Shenzhen Eye Hospital, Shenzhen Eye Medical Center, Southern Medical University, Shenzhen, China
| | - Xinrong Xu
- Department of Ophthalmology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Xinya Hu
- Shenzhen Eye Hospital, Shenzhen Eye Medical Center, Southern Medical University, Shenzhen, China
| | - Weihua Yang
- Shenzhen Eye Hospital, Shenzhen Eye Medical Center, Southern Medical University, Shenzhen, China
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Flindris K, Lagkada V, Christodoulou A, Gazouli M, Moschos M, Markozannes G, Kitsos G. Investigation of UCHL3 and HNMT Gene Polymorphisms in Greek Patients with Type 2 Diabetes Mellitus and Diabetic Retinopathy. Biomedicines 2025; 13:341. [PMID: 40002753 PMCID: PMC11852632 DOI: 10.3390/biomedicines13020341] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2025] [Revised: 01/30/2025] [Accepted: 01/31/2025] [Indexed: 02/27/2025] Open
Abstract
BACKGROUND AND OBJECTIVES Recent studies have shed light on the association between genetic factors and diabetic retinopathy (DR) onset and progression. The purpose of our study was to investigate the association between rs4885322 single-nucleotide polymorphism (SNP) of the UCHL3 gene and rs11558538 SNP of the HNMT gene with the risk of DR in Greek patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS In our case-control study, we included 85 T2DM patients with DR and 71 T2DM patients without DR (NDR), matched by ethnicity and gender. Demographic and clinical data of all patients were collected, and then patients went through a complete ophthalmological examination and were genotyped for rs4885322 SNP of UCHL3 gene and for the rs11558538 SNP of HNMT gene. Statistical analysis was implemented by STATA v.16.1. RESULTS No significant differences in demographic and clinical data were observed between the DR and the NDR group (p-value ≥ 0.05), except for the lower mean of age, longer duration of DM, more frequent use of insulin therapy, and higher levels of hemoglobin A1c (HbA1c) in the DR group. The allelic effect of rs488532 increases the risk of DR by 2.04 times, and in the dominant genetic model, the risk of DR is elevated by 123%, while both associations are statistically significant (p-value < 0.05). Moreover, the allelic effect of rs11558538 is associated with a 3.27 times increased DR risk and, in the dominant genetic model, reveals an augmented risk of DR by 231%, while both associations are also statistically significant (p-value < 0.05). CONCLUSIONS The rs4885322 SNP of the UCHL3 gene and the rs11558538 SNP of the HNMT gene are associated with DR risk in Greek patients with T2DM. However, further studies with larger samples and different ethnicities should be implemented to clarify the exact association of these SNPs and DR onset.
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Affiliation(s)
- Konstantinos Flindris
- Department of Ophthalmology, University General Hospital of Ioannina, 45500 Ioannina, Greece; (A.C.); (G.K.)
| | - Vivian Lagkada
- Laboratory of Biology, Department of Basic Medical Sciences, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece; (V.L.); (M.G.)
| | - Aikaterini Christodoulou
- Department of Ophthalmology, University General Hospital of Ioannina, 45500 Ioannina, Greece; (A.C.); (G.K.)
| | - Maria Gazouli
- Laboratory of Biology, Department of Basic Medical Sciences, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece; (V.L.); (M.G.)
| | - Marilita Moschos
- 1st Department of Ophthalmology, University of Athens, 11527 Athens, Greece;
| | - Georgios Markozannes
- Department of Hygiene and Epidemiology, Medical School, University of Ioannina, 45500 Ioannina, Greece;
| | - George Kitsos
- Department of Ophthalmology, University General Hospital of Ioannina, 45500 Ioannina, Greece; (A.C.); (G.K.)
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Kikushima W, Furuhata Y, Shijo T, Matsumoto M, Sakurada Y, Viel Tsuru D, Kashiwagi K. Comparison of one-year real-world outcomes between red (670 nm) subthreshold micropulse laser treatment and intravitreal aflibercept injection for treatment-naïve diabetic macular edema. Photodiagnosis Photodyn Ther 2025; 51:104430. [PMID: 39645014 DOI: 10.1016/j.pdpdt.2024.104430] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Revised: 11/11/2024] [Accepted: 12/02/2024] [Indexed: 12/09/2024]
Abstract
PURPOSE To evaluate the treatment outcomes of subthreshold micropulse laser (SMPL) with a wavelength of 670 nm (red) for treatment-naïve diabetic macular edema (DME). METHODS A retrospective observational study which included 42 eyes in 34 patients diagnosed with treatment-naïve DME was conducted. Twenty-one eyes underwent red SMPL and the other 21 eyes underwent intravitreal injection of aflibercept (IVA) as initial treatment and were followed up for 12 months. Best-corrected visual acuity (BCVA), central retinal thickness (CRT) on optical coherence tomography (OCT), vessel density (VD), and foveal avascular zone area on OCT angiography (OCTA) were measured and compared between the two groups. RESULTS In the red SMPL group, the mean BCVA slightly improved from 0.29 ± 0.28 at baseline to 0.22 ± 0.29 at 12 months (p = 0.18), while the mean CRT significantly decreased from 472 ± 200 µm at baseline to 320 ± 136 µm at 12 months (p = 0.003). At 12 months from baseline, the mean change in BCVA and CRT were similar between the red SMPL and IVA groups (p = 0.79 and p = 0.31, respectively). No significant change was detected in OCTA parameters except for VD at the nasal section in the red SMPL group. CONCLUSION Red SMPL for treatment-naïve DME maintained BCVA and significantly reduced CRT at 12 months. These treatment outcomes were equivalent to IVA in real-world settings, which tend to be inferior to clinical trials.
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Affiliation(s)
- Wataru Kikushima
- Department of Ophthalmology, University of Yamanashi, Shimokato 1110, Chuo, Yamanashi Prefecture, Japan.
| | - Yukiko Furuhata
- Department of Ophthalmology, University of Yamanashi, Shimokato 1110, Chuo, Yamanashi Prefecture, Japan
| | - Taiyo Shijo
- Department of Ophthalmology, University of Yamanashi, Shimokato 1110, Chuo, Yamanashi Prefecture, Japan
| | - Mizuki Matsumoto
- Department of Ophthalmology, University of Yamanashi, Shimokato 1110, Chuo, Yamanashi Prefecture, Japan
| | - Yoichi Sakurada
- Department of Ophthalmology, University of Yamanashi, Shimokato 1110, Chuo, Yamanashi Prefecture, Japan
| | - Daphne Viel Tsuru
- Department of Ophthalmology, University of Yamanashi, Shimokato 1110, Chuo, Yamanashi Prefecture, Japan
| | - Kenji Kashiwagi
- Department of Ophthalmology, University of Yamanashi, Shimokato 1110, Chuo, Yamanashi Prefecture, Japan
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Ayoub S, Tanweer H, Javaid HA, Khan MN, Ahmed S, Eljack MMF. Bridging the Gap: The Role of Continuous Positive Airway Pressure Therapy in Diabetic Retinopathy Associated With Obstructive Sleep Apnea-A Perspective. Health Sci Rep 2025; 8:e70502. [PMID: 39995799 PMCID: PMC11847710 DOI: 10.1002/hsr2.70502] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2024] [Revised: 01/29/2025] [Accepted: 02/07/2025] [Indexed: 02/26/2025] Open
Abstract
Background Obstructive sleep apnea (OSA) is a highly prevalent, yet under-diagnosed sleep disorder and has a strong association with type 2 diabetes and diabetic retinopathy (DR). Vascular abnormalities, nocturnal glucose dysregulation, impaired blood flow, and hypoxia during OSA induce oxidative stress and promote the inflammatory pathways which increase the VEGF factor levels, leading to the progression of DR. Aims To date, continuous positive airway pressure (CPAP) is the most effective, gold-standard treatment for patients with moderate to severe OSA. However, the implications of CPAP for the treatment of DR due to OSA is still a topic of ongoing debate. Conclusion Evidence suggests that the administration of CPAP therapy led to a reduction in retinal exudates and optical coherence tomography indices for retinal edema and also exhibited improvement in glycemic control, sleepiness, and overall health-related quality of life. Nevertheless, there are limited studies present that have evaluated the impact of CPAP therapy on DR in patients with OSA and well-designed studies are needed to confirm CPAP's therapeutic effect on DR despite these findings. Moreover, concerns regarding its long-term safety, adherence challenges, and inconsistent study designs limit definitive conclusions about CPAP's efficacy in managing DR. This indicates the need for future studies to advocate for enhanced CPAP adherence strategies, refined diagnostic criteria for OSA, and large-scale clinical trials to explore CPAP's therapeutic role in DR. Addressing these challenges could revolutionize clinical practices, optimize patient outcomes, and establish CPAP as a cornerstone in the integrated management of OSA and DR.
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Affiliation(s)
- Sadia Ayoub
- Jinnah Sindh Medical UniversityKarachiPakistan
| | | | | | | | - Shahzaib Ahmed
- Department of MedicineFatima Memorial Hospital College of Medicine and DentistryLahorePakistan
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Thacker M, Wong KY, Zhou L, Liu J, Wong MS. Exploring ocular disorders in Parkinson's disease: A comprehensive review and future perspectives. Exp Eye Res 2025; 251:110225. [PMID: 39725258 DOI: 10.1016/j.exer.2024.110225] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2024] [Revised: 12/21/2024] [Accepted: 12/22/2024] [Indexed: 12/28/2024]
Abstract
Parkinson's disease (PD) is a multifaceted neurodegenerative disorder characterized by predominantly motor symptoms. However, recent research has broadened our understanding of PD by revealing its impact on non-motor functions, including ocular manifestations. This review explored the intricate relationship between PD and ocular health, shedding light on the mechanisms underlying common ocular diseases such as dry eye disease, cataract, glaucoma, age-related macular degeneration, and diabetic retinopathy. It also underscores the importance of recognizing ocular manifestations as potential early markers of PD, as well as their impact on patients' daily activities, necessitating prompt identification and intervention to prevent complications and enhance the overall quality of life. Furthermore, future research should prioritize unraveling the potential association between PD and other prevalent ocular diseases, such as myopia, to formulate effective treatment strategies.
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Affiliation(s)
- Minal Thacker
- Centre for Eye and Vision Research (CEVR), 17W Hong Kong Science Park, Hong Kong
| | - Ka Ying Wong
- Centre for Eye and Vision Research (CEVR), 17W Hong Kong Science Park, Hong Kong; Department of Chemistry, Waterloo Institute for Nanotechnology, University of Waterloo, Waterloo, ON, N2L 3G1, Canada
| | - Liping Zhou
- Centre for Eye and Vision Research (CEVR), 17W Hong Kong Science Park, Hong Kong; School of Optometry, The Hong Kong Polytechnic University, Kowloon, Hong Kong; Research Centre for Chinese Medicine Innovation, The Hong Kong Polytechnic University, Kowloon, Hong Kong; Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Kowloon, Hong Kong.
| | - Juewen Liu
- Centre for Eye and Vision Research (CEVR), 17W Hong Kong Science Park, Hong Kong; Department of Chemistry, Waterloo Institute for Nanotechnology, University of Waterloo, Waterloo, ON, N2L 3G1, Canada
| | - Man-Sau Wong
- Centre for Eye and Vision Research (CEVR), 17W Hong Kong Science Park, Hong Kong; Research Centre for Chinese Medicine Innovation, The Hong Kong Polytechnic University, Kowloon, Hong Kong; Department of Food Science and Nutrition, The Hong Kong Polytechnic University, Kowloon, Hong Kong.
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Liu J, Wang H, Huang C. Exendin-4, a GLP-1 receptor agonist, suppresses diabetic retinopathy in vivo and in vitro. Arch Physiol Biochem 2025; 131:1-10. [PMID: 37920998 DOI: 10.1080/13813455.2023.2274279] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Accepted: 10/18/2023] [Indexed: 11/04/2023]
Abstract
Diabetic retinopathy (DR) is a complication of diabetes and a leading cause of blindness in adults. Studies have shown that glucagon-like peptide-1 (GLP-1) exerts a protective effect on patients with DR. Here, we investigated the protective effects of Exendin-4, a GLP-1 analogue, on DR. We established a high-glucose-induced HREC cell model and an STZ-induced rat DR Model to study the effect of Exendin-4 in DR in vitro and in vivo. The qRT-PCR, CCK-8, TUNEL, western blotting, tube formation assays, and ELISA were performed. In addition, we overexpressed TGFB2 to observe whether the protective effect of Exendin-4 was reversed. Our results showed that Exendin-4 inhibited the progression of DR. Furthermore, the protective effect of Exendin-4 was suppressed in cells overexpressing TGFB2. Our findings suggest that Exendin-4 may be involved in the regulation of TGFB2 expression levels to inhibit DR. These results indicate that Exendin-4 could be an effective therapy for DR.
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Affiliation(s)
- Jufen Liu
- Ophthalmology Department of Shangyu People's Hospital of Shaoxing City, Shaoxing, China
| | - Huijing Wang
- Health Management Center of Shangyu People's Hospital of Shaoxing City, Shaoxing, China
| | - Cuiting Huang
- Ophthalmology Department Of Ningde City Hospital, Ningde Normal University, China
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Młynarska E, Czarnik W, Dzieża N, Jędraszak W, Majchrowicz G, Prusinowski F, Stabrawa M, Rysz J, Franczyk B. Type 2 Diabetes Mellitus: New Pathogenetic Mechanisms, Treatment and the Most Important Complications. Int J Mol Sci 2025; 26:1094. [PMID: 39940862 PMCID: PMC11817707 DOI: 10.3390/ijms26031094] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Revised: 01/19/2025] [Accepted: 01/22/2025] [Indexed: 02/16/2025] Open
Abstract
Type 2 diabetes mellitus (T2DM), a prevalent chronic disease affecting over 400 million people globally, is driven by genetic and environmental factors. The pathogenesis involves insulin resistance and β-cell dysfunction, mediated by mechanisms such as the dedifferentiation of β-cells, mitochondrial dysfunction, and oxidative stress. Treatment should be based on non-pharmacological therapy. Strategies such as increased physical activity, dietary modifications, cognitive-behavioral therapy are important in maintaining normal glycemia. Advanced therapies, including SGLT2 inhibitors and GLP-1 receptor agonists, complement these treatments and offer solid glycemic control, weight control, and reduced cardiovascular risk. Complications of T2DM, such as diabetic kidney disease, retinopathy, and neuropathy, underscore the need for early diagnosis and comprehensive management to improve patient outcomes and quality of life.
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Affiliation(s)
- Ewelina Młynarska
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Witold Czarnik
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Natasza Dzieża
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Weronika Jędraszak
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Gabriela Majchrowicz
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Filip Prusinowski
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Magdalena Stabrawa
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Jacek Rysz
- Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Beata Franczyk
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
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22
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Banks J, Olvera-Barrios A, Pitt M, Williams D, Seltene M, Rutowska C, Khatun M, Huemer J, Khan Y, Ockrim Z, Heng LZ, Rudnicka AR, Tufail A, A Egan C, Owen CG. Effect of ethnicity and other sociodemographic factors on attendance at ophthalmology appointments following referral from a Diabetic Eye Screening Programme: a retrospective cohort study. BMJ Open Ophthalmol 2025; 10:e001969. [PMID: 39843349 PMCID: PMC11759212 DOI: 10.1136/bmjophth-2024-001969] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Accepted: 11/15/2024] [Indexed: 01/24/2025] Open
Abstract
BACKGROUND/AIMS To examine the association between sociodemographic characteristics and attendance at Hospital Eye Service (HES) referrals from the Diabetic Eye Screening Programme (DESP), in a large, ethnically diverse urban population. METHODS Retrospective cohort study (4 January 2016-12 August 2019) of people with diabetic retinopathy (DR) referred from an English DESP to a tertiary referral eye hospital. We conducted a multivariable logistic regression with attendance as the primary outcome, controlling for age, sex, ethnicity, Index of Multiple Deprivation, best eye visual acuity and baseline DR grade. RESULTS Of 7793 people referred (mean age 64 years, 62.6% male, 13.9% white, 12.5% black, 25.3% South Asian, 6.5% any other Asian background, 19.3% no recorded ethnicity and 20.9% of 'Other' ethnic origin), 69% attended. Compared with white individuals, people of black ethnic origin were similarly likely to attend. South Asians and those of other Asian backgrounds were more likely, and people with 'Other' or missing ethnicity were less likely to attend. Those with higher levels of deprivation, younger (aged 18-45 years) and older (76-90 years) age groups and worse visual acuity were less likely to attend, whereas people identified as having proliferative DR in both eyes were more likely to attend. CONCLUSION Sociodemographic patterns in attendance after referral from the DESP to the HES exist, and these do not appear to explain ethnic differences in more severe sight-threatening DR, suggesting other explanations. More work is needed to understand and reduce inequalities in HES attendance.
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Affiliation(s)
- James Banks
- Population Health Research Institute, City St George's, University of London , London, UK
| | - Abraham Olvera-Barrios
- Medical Retina, Moorfields Eye Hospital NHS Foundation Trust, London, UK
- NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK
| | - Matilda Pitt
- Population Health Research Institute, City St George's, University of London , London, UK
| | - Daisy Williams
- Population Health Research Institute, City St George's, University of London , London, UK
| | - Michael Seltene
- Medical Retina, Moorfields Eye Hospital NHS Foundation Trust, London, UK
| | - Celestine Rutowska
- Medical Retina, Moorfields Eye Hospital NHS Foundation Trust, London, UK
| | - Mumina Khatun
- Medical Retina, Moorfields Eye Hospital NHS Foundation Trust, London, UK
| | - Josef Huemer
- Medical Retina, Moorfields Eye Hospital NHS Foundation Trust, London, UK
- NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK
| | - Yasir Khan
- Medical Retina, Moorfields Eye Hospital NHS Foundation Trust, London, UK
| | - Zoe Ockrim
- Medical Retina, Moorfields Eye Hospital NHS Foundation Trust, London, UK
| | - Ling Zhi Heng
- Medical Retina, Moorfields Eye Hospital NHS Foundation Trust, London, UK
| | - Alicja R Rudnicka
- Population Health Research Institute, City St George's, University of London , London, UK
| | - Adnan Tufail
- Medical Retina, Moorfields Eye Hospital NHS Foundation Trust, London, UK
- NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK
| | - Catherine A Egan
- Medical Retina, Moorfields Eye Hospital NHS Foundation Trust, London, UK
- NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK
| | - Christopher G Owen
- Population Health Research Institute, City St George's, University of London , London, UK
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23
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Pushparani DS, Varalakshmi J, Roobini K, Hamshapriya P, Livitha A. Diabetic Retinopathy-A Review. Curr Diabetes Rev 2025; 21:43-55. [PMID: 38831577 DOI: 10.2174/0115733998296228240521151050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2024] [Revised: 04/21/2024] [Accepted: 04/30/2024] [Indexed: 06/05/2024]
Abstract
Diabetic Retinopathy is a vascular microvascular disease also called diabetic eye disease caused by microangiopathy leading to progressive damage of the retina and blindness. The uncontrolled blood glycemic level or sugar level results in diabetic retinopathy. There are two stages of diabetic retinopathy: proliferative diabetic retinopathy and nonproliferative diabetic retinopathy. Symptoms of diabetic retinopathy often have no early warning signs, even muscular edema, which can cause rapid vision loss. Macular edema in which the blood vessels leak can also occur at any stage of diabetic retinopathy. Symptoms are darkened or distorted images and blurred vision that are not the same in both eyes. This review study primarily discusses the pathophysiology, genetics, and ALR, AGEs, VEGF, EPO, and eNOS involved in diabetic retinopathy. The longer a person has diabetes, the higher their risk of developing some ocular problems. During pregnancy, diabetic retinopathy may also be a problem for women with diabetes. NIH are recommends that all pregnant women with diabetes have an overall eye examination. Diagnosis of diabetic retinopathy is made during an eye examination that comprises ophthalmoscopy or fundus photography, and glow-in angiography for Fundus. Here, we present a review of the current insights into pathophysiology in diabetic retinopathy, as well as clinical treatments for diabetic retinopathy patients. Novel laboratory findings and related clinical trials are also analysed.
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Affiliation(s)
- D S Pushparani
- PG and Research Department of Biochemistry, Dwaraka Doss Goverdhan Doss Vaishnav College, Arumbakkam, Chennai, 600106, India
| | - J Varalakshmi
- PG and Research Department of Biochemistry, Dwaraka Doss Goverdhan Doss Vaishnav College, Arumbakkam, Chennai, 600106, India
| | - K Roobini
- PG and Research Department of Biochemistry, Dwaraka Doss Goverdhan Doss Vaishnav College, Arumbakkam, Chennai, 600106, India
| | - P Hamshapriya
- PG and Research Department of Biochemistry, Dwaraka Doss Goverdhan Doss Vaishnav College, Arumbakkam, Chennai, 600106, India
| | - A Livitha
- PG and Research Department of Biochemistry, Dwaraka Doss Goverdhan Doss Vaishnav College, Arumbakkam, Chennai, 600106, India
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24
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Xiaojing S, Li M. Construction of novel 10 signatures in diabetic retinopathy construction of model based on WGCNA: Mechanism of action of RPL3 and MRPL16 protein. Int J Biol Macromol 2025; 286:138235. [PMID: 39617243 DOI: 10.1016/j.ijbiomac.2024.138235] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Revised: 11/20/2024] [Accepted: 11/29/2024] [Indexed: 12/09/2024]
Abstract
Diabetic retinopathy is a common microvascular complication in diabetic patients, which can lead to blindness in severe cases. At present, although a variety of treatment methods are available, the pathological mechanism has not been fully elucidated. As ribosomal proteins, RPL3 and MRPL16 play important roles in cell metabolism and protein synthesis, but their specific roles in diabetic retinopathy are unclear. This study aims to construct new features of diabetic retinopathy by WGCNA method, and reveal the mechanism of RPL3 and MRPL16 protein in diabetic retinopathy, so as to provide new ideas for the early diagnosis and treatment of diabetic retinopathy. The study collected retinal tissue samples from patients with diabetic retinopathy and used high-throughput sequencing techniques to obtain gene expression data. Gene expression data were analyzed by WGCNA method to construct the characteristic module of diabetic retinopathy. On this basis, the genes significantly associated with diabetic retinopathy were screened out, and the mechanism of action of RPL3 and MRPL16 proteins in diabetic retinopathy was studied through bioinformatics analysis and experimental verification. Through WGCNA analysis, we successfully constructed a characteristic module of diabetic retinopathy and screened out genes significantly associated with the disease. Further studies have shown that RPL3 and MRPL16 proteins are up-regulated in diabetic retinopathy and play key roles in cell metabolism and protein synthesis. Through in vitro experiments and animal model verification, we found that the abnormal expression of RPL3 and MRPL16 proteins is closely related to the pathological process of diabetic retinopathy.
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Affiliation(s)
- Sun Xiaojing
- Department of Ophthalmology, First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Ma Li
- Department of Ophthalmology, First Affiliated Hospital of Dalian Medical University, Dalian 116011, China.
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25
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Jia J, Liu B, Wang X, Ji F, Wen F, Song L, Xu H, Ding T. Network Pharmacology and Molecular Docking to Explore the Mechanism of Compound Qilian Tablets in Treating Diabetic Retinopathy. Curr Comput Aided Drug Des 2025; 21:333-347. [PMID: 40420737 DOI: 10.2174/0115734099298932240308104437] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Revised: 02/26/2024] [Accepted: 02/28/2024] [Indexed: 05/28/2025]
Abstract
BACKGROUND Diabetic Retinopathy (DR) is one of the common chronic complications of diabetes mellitus, which has developed into the leading cause of irreversible visual impairment in adults worldwide. The Compound Qilian Tablets (CQLT) were developed in China for the treatment and prevention of DR, but their mechanism of action still needs to be clarified. OBJECTIVES In the present study, network pharmacology, molecular docking, and in vivo validation experiments were used to investigate the active components and molecular mechanisms of CQLT against DR. METHODS The active components and targets of CQLT were collected through the TCSMP database, and the targets of DR were obtained from GeneCards, OMIM, and Drugbank databases. We established a protein-protein interaction network using the STRING database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using the Metascape database. Molecular docking using AutoDock Vina was performed to investigate the interactions between components of CQLT and core targets. Moreover, we selected ZDF rats to establish a DR model for the experimental studies. RESULTS 39 active components and 448 targets in CQLT were screened, among which 90 targets were shared with DR. KEGG pathway enrichment analysis identified 181 pathways. The molecular docking results demonstrated that the main active components had strong binding ability to the core targets. The results from animal experiments indicate that the mechanism of CQLT against DR is associated with inhibiting the retinal mTOR/HIF-1α/VEGF signaling pathway, alleviating the inflammatory response, suppressing retinal neovascularization, and protecting the function and morphology of the retina. CONCLUSION The present study preliminarily explored the mechanism of CQLT in treating DR and demonstrated that CQLT exerts anti-DR effects through multiple components, multiple targets, and multiple pathways. These findings suggest that CQLT shows promise as a potential therapeutic agent for DR and could contribute to developing novel treatments.
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Affiliation(s)
- Jiangwei Jia
- Pharmacodynamic and Toxicological Evaluation Center, Jilin Academy of Chinese Medicine Sciences, Changchun, Jilin, China
- School of Pharmaceutical Sciences, Changchun University of Chinese Medicine, Changchun, Jilin, China
| | - Bo Liu
- Pharmacodynamic and Toxicological Evaluation Center, Jilin Academy of Chinese Medicine Sciences, Changchun, Jilin, China
| | - Xin Wang
- Pharmacodynamic and Toxicological Evaluation Center, Jilin Academy of Chinese Medicine Sciences, Changchun, Jilin, China
| | - Fenglan Ji
- Pharmacodynamic and Toxicological Evaluation Center, Jilin Academy of Chinese Medicine Sciences, Changchun, Jilin, China
| | - Fuchun Wen
- Pharmacodynamic and Toxicological Evaluation Center, Jilin Academy of Chinese Medicine Sciences, Changchun, Jilin, China
| | - Lianlian Song
- Pharmacodynamic and Toxicological Evaluation Center, Jilin Academy of Chinese Medicine Sciences, Changchun, Jilin, China
| | - Huibo Xu
- Pharmacodynamic and Toxicological Evaluation Center, Jilin Academy of Chinese Medicine Sciences, Changchun, Jilin, China
| | - Tao Ding
- Pharmacodynamic and Toxicological Evaluation Center, Jilin Academy of Chinese Medicine Sciences, Changchun, Jilin, China
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26
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Newman D, Warren B, Barker R, Wykoff CC, Vujosevic S. Patient and Physician Perspectives of Diabetic Retinopathy and Diabetic Macular Edema Diagnosis, Treatment and Progression: A Podcast Article. Ophthalmol Ther 2025; 14:1-12. [PMID: 39503993 PMCID: PMC11724807 DOI: 10.1007/s40123-024-01053-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2024] [Accepted: 10/04/2024] [Indexed: 01/12/2025] Open
Abstract
Diabetic retinopathy (DR) is one of the leading causes of vision loss among people of working age. However, people with diabetes are often unaware of the importance of DR screening for preserving vision, highlighting the importance of patient education about DR and DR-related ocular and systemic comorbidities. In this podcast, three patients with different stages of DR and two ophthalmologists exchanged their views on diagnosis, treatment, and progression of DR and diabetic macular edema. The discussion revealed that DR affects not only the physical aspects of patients' lives but also their mental wellbeing. The challenges of a DR diagnosis can be compounded by communication gaps that exist between patients, physicians, and the pharmaceutical industry. Development of new therapies is currently informed mainly by physician perspectives. However, the large burden of current treatments calls for new therapeutic approaches that meet patients' needs better. The preferred method of treatment administration can differ from patient to patient and the choices between treatments that necessitate repeated visits, monitoring, and at-home care must be discussed. As such, going forward it is crucial to consider both the physician and patient perspectives in shaping the clinical landscape of DR.
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Affiliation(s)
| | | | | | - Charles C Wykoff
- Retina Consultants of Texas, Retina Consultants of America, Blanton Eye Institute, Houston Methodist Hospital, Houston, TX, USA
| | - Stela Vujosevic
- Department of Biomedical Surgical and Dental Sciences, University of Milan, Milan, Italy.
- Eye Clinic, IRCCS MultiMedica, Milan, Italy.
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27
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Xi X, Liu X, Chen Q, Ma J, Wang X, Gui Y, Zhang Y, Li Y. Acteoside relieves diabetic retinopathy through the inhibition of Müller cell reactive hyperplasia by regulating TXNIP and mediating Kir4.1 channels in a PI3K/Akt-dependent manner. PLoS One 2024; 19:e0312565. [PMID: 39689088 DOI: 10.1371/journal.pone.0312565] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Accepted: 10/08/2024] [Indexed: 12/19/2024] Open
Abstract
Diabetic retinopathy (DR) is a severe microangiopathy of diabetes. Müller cells play an important role in the development of DR. Acteoside (ACT) has been reported to be effective in the treatment of DR. In this study, we explored the molecular mechanism of ACT in the treatment of DR from the perspective of the reactive proliferation of Müller cells. The effect of ACT on DR was investigated via high-glucose (HG) treatment of Müller RMC-1 cells and an injection of streptozotocin (STZ) in constructed DR cells and animal models. The results showed that after ACT treatment, damage to the retinal structure in DR rats was alleviated, the number of hemangiomas was reduced, and the penetration of blood vessels was weakened. In addition, ACT treatment improved the hypertrophy and gliogenesis of Müller cells during DR, promoted the expression of Kir4.1 and activated the PI3K/Akt signaling pathway. ACT treatment inhibited the proliferation and migration of RMC-1 cells and promoted the expression of Kir4.1. TXNIP overexpression effectively reversed the inhibitory effect of ACT on the proliferation and migration of Müller cells and its induction of Kir4.1 expression. In addition, TXNIP knockdown effectively reversed the inhibitory effect of HG on the expression of p-PI3K and p-Akt, whereas TXNIP overexpression had the opposite effect, and treatment with the PI3K/AKT pathway inhibitor LY294002 effectively reversed the effect of TXNIP knockdown. Animal experiments also confirmed that the therapeutic effect of ACT on DR rats could be reversed by the overexpression of TXNIP or LY294002. In conclusion, ACT inhibits Müller cell reactive proliferation and alleviates diabetic retinopathy by regulating TXNIP and mediating the expression of Kir4.1 channels in a PI3K/Akt-dependent manner.
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Affiliation(s)
- Xiaoting Xi
- Ophthalmology Department, The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Xiaolei Liu
- Neurology Department, The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Qianbo Chen
- Ophthalmology Department, The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Jia Ma
- Ophthalmology Department, The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Xuewei Wang
- Ophthalmology Department, The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Yufei Gui
- Ophthalmology Department, The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Yuxin Zhang
- Ophthalmology Department, The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Yan Li
- Ophthalmology Department, The First Affiliated Hospital of Kunming Medical University, Kunming, China
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28
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Diress M, Wagle SR, Lim P, Foster T, Kovacevic B, Ionescu CM, Mooranian A, Al-Salami H. Advanced drug delivery strategies for diabetic retinopathy: current therapeutic advancement, and delivery methods overcoming barriers, and experimental modalities. Expert Opin Drug Deliv 2024; 21:1859-1877. [PMID: 39557623 DOI: 10.1080/17425247.2024.2431577] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Accepted: 11/15/2024] [Indexed: 11/20/2024]
Abstract
INTRODUCTION Diabetic retinopathy, a significant trigger for blindness among working age individuals with diabetes, poses a substantial global health challenge. Understanding its underlying mechanisms is pivotal for developing effective treatments. Current treatment options, such as anti-VEGF agents, corticosteroids, laser photocoagulation, and vitreous surgery, have their limitations, prompting the exploration of innovative approaches like nanocapsules based drug-delivery systems. Nanoparticles provide promising solutions to improve drug delivery in ocular medicine, overcoming the complexities of ocular anatomy and existing treatment constraints. AREAS COVERED This review explored advanced therapeutic strategies for diabetic retinopathy, focusing on current medications with their limitations, drug delivery methods, device innovations, and overcoming associated barriers. Through comprehensive review, it aimed to contribute to the discovery of more efficient management strategies for diabetic retinopathy in the future. EXPERT OPINION In the next five to ten years, we expect a revolutionary shift in how diabetic retinopathy is treated. As we deepen our understanding of oxidative stress and metabolic dysfunction, antioxidants with specialised delivery matrices are poised to take center stage in prevention and treatment strategies. Our vision is to create a more integrated approach to diabetic retinopathy management that not only improves patient outcomes but also reduces the risks associated to traditional therapies.
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Affiliation(s)
- Mengistie Diress
- The Biotechnology and Drug Development Research Laboratory, Curtin Medical School & Curtin Health Innovation Research Institute, Curtin University, Bentley, AU, Australia
- Department of Human Physiology, School of Medicine, College of Medicine and Health Sciences University of Gondar, Gondar, Ethiopia
| | - Susbin Raj Wagle
- The Biotechnology and Drug Development Research Laboratory, Curtin Medical School & Curtin Health Innovation Research Institute, Curtin University, Bentley, AU, Australia
| | - Patrick Lim
- The Biotechnology and Drug Development Research Laboratory, Curtin Medical School & Curtin Health Innovation Research Institute, Curtin University, Bentley, AU, Australia
| | - Thomas Foster
- The Biotechnology and Drug Development Research Laboratory, Curtin Medical School & Curtin Health Innovation Research Institute, Curtin University, Bentley, AU, Australia
- Department of Clinical Biochemistry, Pathwest Laboratory Medicine, Royal Perth Hospital, Perth, Australia, Australia
| | - Bozica Kovacevic
- The Biotechnology and Drug Development Research Laboratory, Curtin Medical School & Curtin Health Innovation Research Institute, Curtin University, Bentley, AU, Australia
| | - Corina Mihaela Ionescu
- The Biotechnology and Drug Development Research Laboratory, Curtin Medical School & Curtin Health Innovation Research Institute, Curtin University, Bentley, AU, Australia
| | - Armin Mooranian
- The Biotechnology and Drug Development Research Laboratory, Curtin Medical School & Curtin Health Innovation Research Institute, Curtin University, Bentley, AU, Australia
- School of Pharmacy, University of Otago, Dunedin, Otago, New Zealand
| | - Hani Al-Salami
- The Biotechnology and Drug Development Research Laboratory, Curtin Medical School & Curtin Health Innovation Research Institute, Curtin University, Bentley, AU, Australia
- Medical School, The University of Western Australia, Crawley, AU, Australia
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29
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Srejovic JV, Muric MD, Jakovljevic VL, Srejovic IM, Sreckovic SB, Petrovic NT, Todorovic DZ, Bolevich SB, Sarenac Vulovic TS. Molecular and Cellular Mechanisms Involved in the Pathophysiology of Retinal Vascular Disease-Interplay Between Inflammation and Oxidative Stress. Int J Mol Sci 2024; 25:11850. [PMID: 39519401 PMCID: PMC11546760 DOI: 10.3390/ijms252111850] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Revised: 10/28/2024] [Accepted: 10/30/2024] [Indexed: 11/16/2024] Open
Abstract
Retinal vascular diseases encompass several retinal disorders, including diabetic retinopathy, retinopathy of prematurity, age-related macular degeneration, and retinal vascular occlusion; these disorders are classified as similar groups of disorders due to impaired retinal vascularization. The aim of this review is to address the main signaling pathways involved in the pathogenesis of retinal vascular diseases and to identify crucial molecules and the importance of their interactions. Vascular endothelial growth factor (VEGF) is recognized as a crucial and central molecule in abnormal neovascularization and a key phenomenon in retinal vascular occlusion; thus, anti-VEGF therapy is now the most successful form of treatment for these disorders. Interaction between angiopoietin 2 and the Tie2 receptor results in aberrant Tie2 signaling, resulting in loss of pericytes, neovascularization, and inflammation. Notch signaling and hypoxia-inducible factors in ischemic conditions induce pathological neovascularization and disruption of the blood-retina barrier. An increase in the pro-inflammatory cytokines-TNF-α, IL-1β, and IL-6-and activation of microglia create a persistent inflammatory milieu that promotes breakage of the blood-retinal barrier and neovascularization. Toll-like receptor signaling and nuclear factor-kappa B are important factors in the dysregulation of the immune response in retinal vascular diseases. Increased production of reactive oxygen species and oxidative damage follow inflammation and together create a vicious cycle because each factor amplifies the other. Understanding the complex interplay among various signaling pathways, signaling cascades, and molecules enables the development of new and more successful therapeutic options.
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Affiliation(s)
- Jovana V. Srejovic
- University Clinical Center “Kragujevac”, 34000 Kragujevac, Serbia; (J.V.S.); (S.B.S.); (N.T.P.); (D.Z.T.)
- Department of Ophthalmology, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia
| | - Maja D. Muric
- Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia; (M.D.M.); (V.L.J.)
| | - Vladimir Lj. Jakovljevic
- Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia; (M.D.M.); (V.L.J.)
- Center of Excellence for the Study of Redox Balance in Cardiovascular and Metabolic Disorders, University of Kragujevac, 34000 Kragujevac, Serbia
- Department of Human Pathology, First Moscow State Medical University I.M. Sechenov, Moscow 119435, Russia;
| | - Ivan M. Srejovic
- Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia; (M.D.M.); (V.L.J.)
- Center of Excellence for the Study of Redox Balance in Cardiovascular and Metabolic Disorders, University of Kragujevac, 34000 Kragujevac, Serbia
- Department of Pharmacology, First Moscow State Medical University I.M. Sechenov, Moscow 119435, Russia
| | - Suncica B. Sreckovic
- University Clinical Center “Kragujevac”, 34000 Kragujevac, Serbia; (J.V.S.); (S.B.S.); (N.T.P.); (D.Z.T.)
- Department of Ophthalmology, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia
| | - Nenad T. Petrovic
- University Clinical Center “Kragujevac”, 34000 Kragujevac, Serbia; (J.V.S.); (S.B.S.); (N.T.P.); (D.Z.T.)
- Department of Ophthalmology, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia
| | - Dusan Z. Todorovic
- University Clinical Center “Kragujevac”, 34000 Kragujevac, Serbia; (J.V.S.); (S.B.S.); (N.T.P.); (D.Z.T.)
- Department of Ophthalmology, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia
| | - Sergey B. Bolevich
- Department of Human Pathology, First Moscow State Medical University I.M. Sechenov, Moscow 119435, Russia;
| | - Tatjana S. Sarenac Vulovic
- University Clinical Center “Kragujevac”, 34000 Kragujevac, Serbia; (J.V.S.); (S.B.S.); (N.T.P.); (D.Z.T.)
- Department of Ophthalmology, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia
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30
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Klochkov V, Chan CM, Lin WW. Methylglyoxal: A Key Factor for Diabetic Retinopathy and Its Effects on Retinal Damage. Biomedicines 2024; 12:2512. [PMID: 39595078 PMCID: PMC11592103 DOI: 10.3390/biomedicines12112512] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Revised: 10/24/2024] [Accepted: 10/29/2024] [Indexed: 11/28/2024] Open
Abstract
Background: Diabetic retinopathy is the most common retinal vascular disease, affecting the retina's blood vessels and causing chronic inflammation, oxidative stress, and, ultimately, vision loss. Diabetes-induced elevated glucose levels increase glycolysis, the main methylglyoxal (MGO) formation pathway. MGO is a highly reactive dicarbonyl and the most rapid glycation compound to form endogenous advanced glycation end products (AGEs). MGO can act both intra- and extracellularly by glycating molecules and activating the receptor for AGEs (RAGE) pathway. Conclusions: This review summarizes the sources of MGO formation and its actions on various cell pathways in retinal cells such as oxidative stress, glycation, autophagy, ER stress, and mitochondrial dysfunction. Finally, the detoxification of MGO by glyoxalases is discussed.
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Affiliation(s)
- Vladlen Klochkov
- Graduate Institute of Medical Sciences, Taipei Medical University, Taipei 11031, Taiwan;
- Department of Ophthalmology, Cardinal Tien Hospital, New Taipei City 23148, Taiwan
| | - Chi-Ming Chan
- Department of Ophthalmology, Cardinal Tien Hospital, New Taipei City 23148, Taiwan
- School of Medicine, Fu Jen Catholic University, New Taipei City 242062, Taiwan
| | - Wan-Wan Lin
- Graduate Institute of Medical Sciences, Taipei Medical University, Taipei 11031, Taiwan;
- Department of Pharmacology, College of Medicine, National Taiwan University, Taipei 100233, Taiwan
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Ruan Y, Zhang P, Jia X, Hua S, Yao D. Association of vitamin B6 intake with the risk and prognosis of diabetic retinopathy: a NHANES-based study. Clin Exp Optom 2024; 107:847-856. [PMID: 38194486 DOI: 10.1080/08164622.2023.2300298] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Accepted: 12/22/2023] [Indexed: 01/11/2024] Open
Abstract
CLINICAL RELEVANCE Investigating the role of dietary vitamin B6 intake in the risk and prognosis of diabetic retinopathy (DR) could facilitate the management of DR. BACKGROUND This study aimed to assess the association between dietary vitamin B6 intake and the risk of DR and further explore the association between vitamin B6 intake and mortality in patients with DR. METHODS This retrospective cohort study gained data from the National Health and Nutrition Examination Survey (NHANES) 2005-2006 and 2007-2008. The intake of dietary vitamin B6 was assessed by two 24-h dietary recall interviews. Mortality information in the National Death Index was recorded from the date of survey participation through 31 December 2019. Multivariate regression analyses were employed to assess the association between vitamin B6 intake and the risk of DR, and the association between vitamin B6 intake and the risk of mortality in patients with DR. RESULTS A total of 5559 subjects were included, of which 693 (12.47%) had DR. Among these patients with DR, 429 (61.90%) were survivors. Multivariate analyses showed that the intake of vitamin B6 was negatively associated with the risk of DR (odds ratio = 0.81, 95% confidence level: 0.69-0.95, p = 0.012), and patients with DR with an increased intake of vitamin B6 had a significantly decreased risk of all-cause death (hazard ratio = 0.81, 95% confidence level: 0.66-0.99, p = 0.041) or cardiovascular disease-related death (hazard ratio = 0.76, 95% confidence level: 0.58-0.98, p = 0.037). CONCLUSION The intake of vitamin B6 was negatively associated with the risk of DR, and in patients with DR, a higher intake of vitamin B6 was associated with a lower risk of all-cause death and cardiovascular disease-related death, indicating the possible protective role of increased vitamin B6 intake.
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Affiliation(s)
- Yimeng Ruan
- Department of Ophthalmology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China
| | - Ping Zhang
- Department of Ophthalmology, Ningbo Eye Center Hospital, Ningbo, Zhejiang, China
| | - Xinru Jia
- Department of Ophthalmology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China
| | - Shanshan Hua
- Department of Ophthalmology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China
| | - Dongwei Yao
- Department of Ophthalmology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China
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Yao X, Cao X, Yan Z, Qian X, Qian D, Lin Z. Effectiveness of Internet + E-Coach chronic disease management on blood glucose, lipid levels, liver function, and quality of life in patients with chronic diabetic retinopathy: a comparative study. BMC Ophthalmol 2024; 24:468. [PMID: 39465371 PMCID: PMC11514828 DOI: 10.1186/s12886-024-03737-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2024] [Accepted: 10/21/2024] [Indexed: 10/29/2024] Open
Abstract
OBJECTIVE This study aims to explore the effect of Internet + E-Coach chronic disease system intervention on fasting blood glucose (FPG), 2-hour postprandial blood glucose(2hPG), fasting serum insulin (FINS), triglyceride (TG), alanine transaminase (ALT) and quality of life in patients with chronic diabetic retinopathy. METHODS 208 patients with chronic diabetic retinopathy who were treated in the hospital from March 2021 to March 2023 are chosen and separated into two groups by random number Table 104 patients in the control group received routine continuous intervention, and the research group received Internet + E-Coach chronic disease system intervention. The cognition of disease related knowledge, blood related indicators inflammatory factor levels and improvement of life quality between the two groups before intervention, 6 and 12 months after intervention were compared. RESULTS Before the intervention, the comparison between the two groups in disease related knowledge scores, blood glucose, blood lipid, liver function indicators, inflammatory factor, and low vision quality of life scale (CLVQOL) scores was with P > 0.05. After 6 and 12 months of intervention, the research group had significantly higher scores for basic blood glucose intervention, healthy diet, reasonable exercise, and correct medication use compared to the control group (P < 0.05). FPG, 2hPG, TG and ALT in the research group were lower than those in the control group. FINS were higher in the control group, with P < 0.05. Interleukin-6 (IL-6), tumor necrosis factor (TNF-α), and hypersensitive C-reactive protein (Hs-CRP) in the research group were obviously lower than those in the control group (P < 0.05). The scores of far vision, movement and light perception, adjustment ability, reading and fine work, and daily living ability in the research group were higher than those in the control group, with P < 0.05. CONCLUSION The intervention of Internet + E-Coach chronic disease system can improve the knowledge of chronic diabetic retinopathy patients about their own condition, stabilize the levels of blood sugar, blood lipid and liver function indicators, reduce the inflammatory reaction of the body, and improve the quality of life.
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Affiliation(s)
- Xiaojuan Yao
- Department of Emergency Medicine, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, 214023, China
- Department of Emergency Medicine, Wuxi People's Hospital, Wuxi, China
| | - Xiaodong Cao
- Nursing Department, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Jiangsu, 214023, China
| | - Zhaoxian Yan
- Department of Outpatient and Emergency, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Jiangsu, 214023, China
| | - Xiaoli Qian
- Department of Ward 12A, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, 214023, China
| | - Dan Qian
- Department of Emergency Medicine, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, 214023, China
| | - Zheng Lin
- School of Nursing, Nanjing Medical University, Nanjing, 211166, China.
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Morones J, Pérez M, Muñoz M, Sánchez E, Ávila M, Topete J, Ventura J, Martínez S. Evaluation of the Effect of an α-Adrenergic Blocker, a PPAR-γ Receptor Agonist, and a Glycemic Regulator on Chronic Kidney Disease in Diabetic Rats. Int J Mol Sci 2024; 25:11372. [PMID: 39518925 PMCID: PMC11545748 DOI: 10.3390/ijms252111372] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Revised: 10/03/2024] [Accepted: 10/16/2024] [Indexed: 11/16/2024] Open
Abstract
Diabetic nephropathy (DN) is a globally widespread complication of diabetes mellitus (DM). Research indicates that pioglitazone and linagliptin mitigate the risk of DN by reducing inflammation, oxidative stress, and fibrosis. The role of tamsulosin in DN is less studied, but it may contribute to reducing oxidative stress and inflammatory responses. The protective effects of combining pioglitazone, linagliptin, and tamsulosin on the kidneys have scarcely been investigated. This study examines the individual and combined effects of these drugs on DN in Wistar rats. Diabetic rats were treated with tamsulosin, pioglitazone, and linagliptin for six weeks. We assessed food and water intake, estimated glomerular filtration rate (eGFR), histological markers, urea, creatinine, glucose, NF-κB, IL-1, IL-10, TGF-β, and Col-IV using immunofluorescence and qPCR. The DN group exhibited hyperglycaemia, reduced eGFR, and tissue damage. Tamsulosin and linagliptin improved eGFR, decreased urinary glucose, and repaired tissue damage. Pioglitazone and its combinations restored serum and urinary markers and reduced tissue damage. Linagliptin lowered serum creatinine and tissue injury. In conclusion, tamsulosin, linagliptin, and pioglitazone demonstrated renoprotective effects in DN.
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Affiliation(s)
- Jorge Morones
- Department of Morphology, Basic Sciences Center, Universidad Autónoma de Aguascalientes, Aguascalientes 20100, Mexico; (J.M.); (M.P.); (E.S.); (M.Á.)
| | - Mariana Pérez
- Department of Morphology, Basic Sciences Center, Universidad Autónoma de Aguascalientes, Aguascalientes 20100, Mexico; (J.M.); (M.P.); (E.S.); (M.Á.)
| | - Martín Muñoz
- Department of Chemistry, Basic Sciences Center, Universidad Autónoma de Aguascalientes, Aguascalientes 20100, Mexico;
| | - Esperanza Sánchez
- Department of Morphology, Basic Sciences Center, Universidad Autónoma de Aguascalientes, Aguascalientes 20100, Mexico; (J.M.); (M.P.); (E.S.); (M.Á.)
- Family Medicine Unit 8, Instituto Mexicano del Seguro Social (IMSS), Aguascalientes 20180, Mexico
| | - Manuel Ávila
- Department of Morphology, Basic Sciences Center, Universidad Autónoma de Aguascalientes, Aguascalientes 20100, Mexico; (J.M.); (M.P.); (E.S.); (M.Á.)
| | - Jorge Topete
- Department of Nephrology, Regional General Hospital No. 46, Instituto Mexicano del Seguro Social (IMSS), Guadalajara 44910, Mexico;
| | - Javier Ventura
- Department of Morphology, Basic Sciences Center, Universidad Autónoma de Aguascalientes, Aguascalientes 20100, Mexico; (J.M.); (M.P.); (E.S.); (M.Á.)
| | - Sandra Martínez
- Department of Microbiology, Basic Sciences Center, Universidad Autónoma de Aguascalientes, Aguascalientes 20100, Mexico
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Pöstyéni E, Gábriel R, Kovács-Valasek A. Poly (ADP-Ribose) Polymerase-1 (PARP-1) Inhibitors in Diabetic Retinopathy: An Attractive but Elusive Choice for Drug Development. Pharmaceutics 2024; 16:1320. [PMID: 39458649 PMCID: PMC11510672 DOI: 10.3390/pharmaceutics16101320] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2024] [Revised: 10/03/2024] [Accepted: 10/08/2024] [Indexed: 10/28/2024] Open
Abstract
Owing to its promiscuous roles, poly (ADP-ribose) polymerase-1 (PARP-1) is involved in various neurological disorders including several retinal pathologies. Diabetic retinopathy (DR) is the most common microvascular complication of diabetes mellitus affecting the retina. In the present review, we highlight the importance of PARP-1 participation in pathophysiology of DR and discuss promising potential inhibitors for treatment. A high glucose level enhances PARP-1 expression; PARP inhibitors have gained attention due to their potential therapeutic effects in DR. They target different checkpoints (blocking nuclear transcription factor (NF-κB) activation; oxidative stress protection, influence on vascular endothelial growth factor (VEGF) expression, impacting neovascularization). Nowadays, there are several improved clinical PARP-1 inhibitors with different allosteric effects. Combining PARP-1 inhibitors with other compounds is another promising option in DR treatments. Besides pharmacological inhibition, genetic disruption of the PARP-1 gene is another approach in PARP-1-initiated therapies. In terms of future treatments, the limitations of single-target approaches shift the focus onto combined therapies. We emphasize the importance of multi-targeted therapies, which could be effective not only in DR, but also in other ischemic conditions.
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Affiliation(s)
- Etelka Pöstyéni
- Department of Experimental Zoology and Neurobiology, University of Pécs, Ifjúság útja 6, 7624 Pécs, Hungary; (E.P.); (A.K.-V.)
| | - Róbert Gábriel
- Department of Experimental Zoology and Neurobiology, University of Pécs, Ifjúság útja 6, 7624 Pécs, Hungary; (E.P.); (A.K.-V.)
| | - Andrea Kovács-Valasek
- Department of Experimental Zoology and Neurobiology, University of Pécs, Ifjúság útja 6, 7624 Pécs, Hungary; (E.P.); (A.K.-V.)
- János Szentágothai Research Centre, Ifjúság útja 20, 7624 Pécs, Hungary
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Silva JQ, Cebada AB, Escobar-Morreale H, Chávez LN. Complicaciones crónicas de la diabetes mellitus tipo 1. MEDICINE - PROGRAMA DE FORMACIÓN MÉDICA CONTINUADA ACREDITADO 2024; 14:1064-1071. [DOI: 10.1016/j.med.2024.10.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Li B, Hu L, Zhang S, Li S, Tang W, Chen G. The application and clinical translation of the self-evolving machine learning methods in predicting diabetic retinopathy and visualizing clinical transformation. Front Endocrinol (Lausanne) 2024; 15:1429974. [PMID: 39363895 PMCID: PMC11446766 DOI: 10.3389/fendo.2024.1429974] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Accepted: 08/07/2024] [Indexed: 10/05/2024] Open
Abstract
Objective This study aims to analyze the application and clinical translation value of the self-evolving machine learning methods in predicting diabetic retinopathy and visualizing clinical outcomes. Methods A retrospective study was conducted on 300 diabetic patients admitted to our hospital between January 2022 and October 2023. The patients were divided into a diabetic retinopathy group (n=150) and a non-diabetic retinopathy group (n=150). The improved Beetle Antennae Search (IBAS) was used for hyperparameter optimization in machine learning, and a self-evolving machine learning model based on XGBoost was developed. Value analysis was performed on the predictive features for diabetic retinopathy selected through multifactor logistic regression analysis, followed by the construction of a visualization system to calculate the risk of diabetic retinopathy occurrence. Results Multifactor logistic regression analysis revealed that being male, having a longer disease duration, higher systolic blood pressure, fasting blood glucose, glycosylated hemoglobin, low-density lipoprotein cholesterol, and urine albumin-to-creatinine ratio were risk factors for the development of diabetic retinopathy, while non-pharmacological treatment was a protective factor. The self-evolving machine learning model demonstrated significant performance advantages in early diagnosis and prediction of diabetic retinopathy occurrence. Conclusion The application of the self-evolving machine learning models can assist in identifying features associated with diabetic retinopathy in clinical settings, enabling early prediction of disease occurrence and aiding in the formulation of treatment plans to improve patient prognosis.
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Affiliation(s)
- Binbin Li
- Department of Ophthalmology, Ganzhou people’s Hospital, Ganzhou, China
| | - Liqun Hu
- Department of Ophthalmology, Ganzhou people’s Hospital, Ganzhou, China
| | - Siqing Zhang
- Department of Endocrinology, Ganzhou people’s Hospital, Ganzhou, China
| | - Shaojun Li
- Department of Ophthalmology, Ganzhou people’s Hospital, Ganzhou, China
| | - Wei Tang
- Department of Ophthalmology, Ganzhou people’s Hospital, Ganzhou, China
| | - Guishang Chen
- Department of Ophthalmology, Ganzhou people’s Hospital, Ganzhou, China
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Stepien TL. An Approximate Bayesian Computation Approach for Embryonic Astrocyte Migration Model Reduction. Bull Math Biol 2024; 86:126. [PMID: 39269511 DOI: 10.1007/s11538-024-01354-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2024] [Accepted: 08/27/2024] [Indexed: 09/15/2024]
Abstract
During embryonic development of the retina of the eye, astrocytes, a type of glial cell, migrate over the retinal surface and form a dynamic mesh. This mesh then serves as scaffolding for blood vessels to form the retinal vasculature network that supplies oxygen and nutrients to the inner portion of the retina. Astrocyte spreading proceeds in a radially symmetric manner over the retinal surface. Additionally, astrocytes mature from astrocyte precursor cells (APCs) to immature perinatal astrocytes (IPAs) during this embryonic stage. We extend a previously-developed continuum model that describes tension-driven migration and oxygen and growth factor influenced proliferation and differentiation. Comparing numerical simulations to experimental data, we identify model equation components that can be removed via model reduction using approximate Bayesian computation (ABC). Our results verify experimental studies indicating that the choroid oxygen supply plays a negligible role in promoting differentiation of APCs into IPAs and in promoting IPA proliferation, and the hyaloid artery oxygen supply and APC apoptosis play negligible roles in astrocyte spreading and differentiation.
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Affiliation(s)
- Tracy L Stepien
- Department of Mathematics, University of Florida, Gainesville, FL, USA.
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38
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Fang Y, Wang Q, Li Y, Zeng L, Liu J, Ou K. On implications of somatostatin in diabetic retinopathy. Neural Regen Res 2024; 19:1984-1990. [PMID: 38227526 DOI: 10.4103/1673-5374.390955] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2023] [Accepted: 10/10/2023] [Indexed: 01/17/2024] Open
Abstract
Somatostatin, a naturally produced neuroprotective peptide, depresses excitatory neurotransmission and exerts anti-proliferative and anti-inflammatory effects on the retina. In this review, we summarize the progress of somatostatin treatment of diabetic retinopathy through analysis of relevant studies published from February 2019 to February 2023 extracted from the PubMed and Google Scholar databases. Insufficient neuroprotection, which occurs as a consequence of declined expression or dysregulation of retinal somatostatin in the very early stages of diabetic retinopathy, triggers retinal neurovascular unit impairment and microvascular damage. Somatostatin replacement is a promising treatment for retinal neurodegeneration in diabetic retinopathy. Numerous pre-clinical and clinical trials of somatostatin analog treatment for early diabetic retinopathy have been initiated. In one such trial (EUROCONDOR), topical administration of somatostatin was found to exert neuroprotective effects in patients with pre-existing retinal neurodysfunction, but had no impact on the onset of diabetic retinopathy. Overall, we concluded that somatostatin restoration may be especially beneficial for the growing population of patients with early-stage retinopathy. In order to achieve early prevention of diabetic retinopathy initiation, and thereby salvage visual function before the appearance of moderate non-proliferative diabetic retinopathy, several issues need to be addressed. These include the needs to: a) update and standardize the retinal screening scheme to incorporate the detection of early neurodegeneration, b) identify patient subgroups who would benefit from somatostatin analog supplementation, c) elucidate the interactions of somatostatin, particularly exogenously-delivered somatostatin analogs, with other retinal peptides in the context of hyperglycemia, and d) design safe, feasible, low cost, and effective administration routes.
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Affiliation(s)
- Yanhong Fang
- Department of Ophthalmology, Chongqing University Jiangjin Hospital, Chongqing, China
| | - Qionghua Wang
- Department of Ophthalmology, Chongqing University Jiangjin Hospital, Chongqing, China
| | - Youjian Li
- College of Pharmacy, National & Local Joint Engineering Research Center of Targeted and Innovative Therapeutics, IATTI, Chongqing University of Arts and Sciences, Chongqing, China
| | - Li Zeng
- Shandong Provincial Hospital, Shandong Laboratory Animal Center, Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong Province, China
| | - Jian Liu
- Academic Unit of Ophthalmology, Bristol Medical School, University of Bristol, Bristol, UK
| | - Kepeng Ou
- College of Pharmacy, National & Local Joint Engineering Research Center of Targeted and Innovative Therapeutics, IATTI, Chongqing University of Arts and Sciences, Chongqing, China
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Flindris K, Markozannes G, Moschos M, Gazouli M, Christodoulou A, Tsilidis K, Kitsos G. The Association between ADIPOQ Gene Polymorphisms and Diabetic Retinopathy Risk: A Systematic Review and Meta-Analysis. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:1254. [PMID: 39202535 PMCID: PMC11356243 DOI: 10.3390/medicina60081254] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 06/27/2024] [Revised: 07/14/2024] [Accepted: 07/29/2024] [Indexed: 09/03/2024]
Abstract
Background and Objectives: Recent studies have focused on the association between the risk of diabetic retinopathy (DR) and the rs1501299 and rs2241766 polymorphisms of the ADIPOQ gene; however, their results remain inconclusive. Thus, a systematic review and meta-analysis were carried out to clarify the role of these polymorphisms in the development of DR. Materials and Methods: A systematic search of electronic databases (PubMed, Scopus, and Cochrane Library) was conducted until 25 June 2024, and a reference list of relevant articles was collected, which explored the association between the rs1501299 and rs2241766 polymorphisms of the ADIPOQ gene and the risk of DR. The pooled odds ratios (OR) and 95% confidence intervals (CI) were estimated via random-effects model, and the meta-analysis was implemented by using Review Manager 5.4. Results: In total, 6 out of 182 studies, with 1888 cases (DR) and 2285 controls (without DR), were included in the meta-analysis. A statistically significant association between the rs1501299 polymorphism and the DR risk was recorded in G vs. T in the overall analysis (OR = 0.84, 95% CI = 0.72-0.99, p = <0.05, I2 = 23%, n = 5 studies). Additionally, the summary results in the subgroup analysis according to the control type were as follows: the DR versus diabetes mellitus (DM) control type revealed a statistically significant association in G vs. T: OR = 0.81, 95% CI = 0.67-0.97, p = <0.05, I2 = 27%, n = 4 studies; GG vs. GT: OR = 0.72, 95% CI = 0.53-0.98, p = <0.05, I2 = 49%, n = 4 studies; GG vs. (GT + TT): OR = 0.73, 95% CI = 0.55-0.96, p = <0.05, I2 = 44%, n = 4 studies. No significant association was observed between the rs2241766 polymorphism and the DR risk. Conclusions: The current meta-analysis supports the association between the rs1501299 polymorphism of the ADIPOQ gene and the DR risk in patients with DM.
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Affiliation(s)
- Konstantinos Flindris
- Department of Ophthalmology, University General Hospital of Ioannina, 45500 Ioannina, Greece; (A.C.); (G.K.)
| | - Georgios Markozannes
- Department of Hygiene and Epidemiology, Medical School, University of Ioannina, 45500 Ioannina, Greece; (G.M.); (K.T.)
| | - Marilita Moschos
- 1st Department of Ophthalmology, University of Athens, 11527 Athens, Greece;
| | - Maria Gazouli
- Laboratory of Biology, Department of Basic Medical Sciences, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece;
| | - Aikaterini Christodoulou
- Department of Ophthalmology, University General Hospital of Ioannina, 45500 Ioannina, Greece; (A.C.); (G.K.)
| | - Konstantinos Tsilidis
- Department of Hygiene and Epidemiology, Medical School, University of Ioannina, 45500 Ioannina, Greece; (G.M.); (K.T.)
| | - Georgios Kitsos
- Department of Ophthalmology, University General Hospital of Ioannina, 45500 Ioannina, Greece; (A.C.); (G.K.)
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Wang Y, Miao Y, Wan Q. Association Between Triglyceride-Glucose Index and Waist-To-Hip Ratio with Type 2 Diabetic Retinopathy in the Chinese Population: A Cross-Sectional Study. Endocr Res 2024; 49:203-212. [PMID: 38850265 DOI: 10.1080/07435800.2024.2364719] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2024] [Revised: 05/27/2024] [Accepted: 06/02/2024] [Indexed: 06/10/2024]
Abstract
BACKGROUND The triglyceride-glucose (TyG) index serves as a convenient indicator of insulin resistance, which has been demonstrated to be associated with diabetic retinopathy(DR). However, the relationship between TyG-WHR, a novel index combining TyG with the central obesity indicator WHR, and retinopathy in patients with type 2 diabetes remains unclear. Therefore, this study aims to investigate the correlation between TyG-WHR and DR in adult patients with type 2 diabetes. METHODS This cross-sectional study included 1702 patients with T2DM. Logistic regression analysis was performed to examine the associations between TyG-WHR and DR. Additionally, the receiver operating characteristic curve (ROC curve) was utilized to assess the predictive efficacy of TyG-WHR for DR. RESULTS Patients in higher TyG-WHR quartiles demonstrated an increased presence of DR, and TyG-WHR increased with the severity of DR. Moreover, TyG-WHR remained significantly associated with a higher odds ratio (OR) for DR (OR 1.223, 95% confidence interval [CI] 1.078-1.387, p < 0.05) after multivariate adjustment. Additionally, receiver operating characteristic curve analysis indicated that the optimal cutoff value for TyG-WHR in predicting DR presence was 8.8983, with a sensitivity of 61.00%, specificity of 48.50%, and area under the curve (AUC) of 0.555. CONCLUSIONS In patients with T2DM, TyG-WHR was significantly elevated in those with DR and independently associated with an increased risk of DR presence in Chinese patients. This implies that TyG-WHR could potentially serve as a valuable and dependable biomarker for DR, underscoring the importance of giving greater consideration to T2DM patients with elevated TyG-WHR to effectively prevent and mitigate the onset of DR and associated adverse health outcomes.
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Affiliation(s)
- Yu Wang
- Department of Cardiology, Luzhou People's Hospital, Luzhou, China
| | - Ying Miao
- Department of Endocrinology and Metabolism, Affiliated Hospital of Southwest Medical University, Luzhou, China
- Metabolic Vascular Disease Key Laboratory of Sichuan Province, Luzhou, China
- Sichuan Clinical Research Center for Diabetes and Metabolism, Luzhou, China
- Sichuan Clinical Research Center for Nephropathy, Luzhou, China
- Cardiovascular and Metabolic Diseases Key Laboratory of Luzhou, Luzhou, China
- Southwest Medical University, Luzhou, China
| | - Qin Wan
- Department of Endocrinology and Metabolism, Affiliated Hospital of Southwest Medical University, Luzhou, China
- Metabolic Vascular Disease Key Laboratory of Sichuan Province, Luzhou, China
- Sichuan Clinical Research Center for Diabetes and Metabolism, Luzhou, China
- Sichuan Clinical Research Center for Nephropathy, Luzhou, China
- Cardiovascular and Metabolic Diseases Key Laboratory of Luzhou, Luzhou, China
- Southwest Medical University, Luzhou, China
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Wang S, Jia B, Niu S, Chen S. Relationship Between the Hemoglobin, Albumin, Lymphocyte Count, Platelet Count (HALP) Score and Type 2 Diabetes Retinopathy. Diabetes Metab Syndr Obes 2024; 17:2693-2706. [PMID: 39007156 PMCID: PMC11246656 DOI: 10.2147/dmso.s467799] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2024] [Accepted: 06/21/2024] [Indexed: 07/16/2024] Open
Abstract
Purpose To explore the correlation between hemoglobin, albumin, lymphocyte count, platelet count (HALP) score and type 2 diabetic retinopathy (DR). Methods The study was conducted on 674 patients with type 2 diabetes (T2DM). According to the results of the fundus examination, they were divided into non-diabetic retinopathy group (NDR, n=388) and diabetic retinopathy group (DR, n=286). Collected patients baseline data, calculated HALP score, analyzed the correlation between HALP score and DR. Results In all patients, male patients and female patients, the HALP score of the DR group was lower than that of the NDR group (P<0.001), and the HALP score was negatively correlated with the incidence of DR (P<0.05). HALP score was independent risk factors for DR, regardless of gender. In male patients, HALP score and DR had a linear relationship, but in female patients, HALP score and DR showed a nonlinear relationship, and HALP score was more sensitive to the onset of DR in male patients. The combined diagnostic model of HALP score, course of disease, SBP and BUN was used to diagnose DR, and it was found that the diagnostic value was the highest among male patients, with AUC of 0.761, sensitivity of 58.3% and specificity of 80.3%. Conclusion HALP score was an independent risk factor for DR, attention should be paid to monitoring HALP score, especially in male T2DM patients. The accuracy of HALP score, disease course, SBP and BUN combined model diagnosis of DR was high, which can become a biological indicator for early screening of DR.
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Affiliation(s)
- Shuqi Wang
- Department of Internal Medicine, Hebei Medical University, Shijiazhuang, People's Republic of China
- Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People's Republic of China
| | - Boying Jia
- Department of Internal Medicine, Hebei Medical University, Shijiazhuang, People's Republic of China
- Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People's Republic of China
| | - Sifan Niu
- Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People's Republic of China
- Department of Internal Medicine, North China University of Science and Technology, Tangshan, People's Republic of China
| | - Shuchun Chen
- Department of Internal Medicine, Hebei Medical University, Shijiazhuang, People's Republic of China
- Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People's Republic of China
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Zhuang Y, Zhuang Z, Cai Q, Hu X, Huang H. Serum vitamin D is substantially reduced and predicts flares in diabetic retinopathy patients. J Diabetes Investig 2024; 15:867-873. [PMID: 38469994 PMCID: PMC11215683 DOI: 10.1111/jdi.14185] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Revised: 02/22/2024] [Accepted: 03/01/2024] [Indexed: 03/13/2024] Open
Abstract
AIMS/INTRODUCTION Research has suggested that vitamin D deficiency is associated with diabetic retinopathy (DR). Our study aimed to determine whether vitamin D deficiency is the cause of diabetic retinopathy or if diabetic retinopathy reduces vitamin D levels. MATERIALS AND METHODS Participants with type-2 diabetes were recruited for this prospective observational clinical study and were divided into a diabetic group without retinopathy and a diabetic group with retinopathy, with additional healthy volunteers serving as a control group. The differences in clinical characteristics among the three groups were also compared. Patients without retinopathy were then followed for 1 year to monitor the incidence of diabetic retinopathy. After follow-up, participants were divided into subgroups based on whether diabetic retinopathy occurred. The baseline data of the subgroups were compared, and the independent risk factors were analyzed. RESULTS Vitamin D levels were generally low. Participants with diabetic retinopathy had significantly lower vitamin D levels than did those without retinopathy (P < 0.01). A comparison of the two subgroups revealed lower baseline vitamin D concentrations in the new-DR subgroup than in the non-DR subgroup (P < 0.01). Vitamin D deficiency and elevated HbA1c levels were found to be independent risk factors for diabetic retinopathy (OR = 0.935, 95% CI: 0.867-0.981, P = 0.006; OR = 2.208, 95% CI: 1.764-2.764, P < 0.01). The limit of vitamin D intake according to the receiver-operating characteristic (ROC) curve was 26.01 ng/mL, and the area under the ROC curve was 0.603 (95% CI: 0.559-0.706, P = 0.002). CONCLUSIONS Vitamin D levels were significantly lower in patients diagnosed with diabetic retinopathy. More importantly, vitamin D deficiency may accelerate the onset of diabetic retinopathy.
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Affiliation(s)
- Yong Zhuang
- Department of EndocrinologyThe Second Affiliated Hospital of Fujian Medical UniversityQuanzhouChina
| | - Zihao Zhuang
- Department of OphthalmologyThe Second Affiliated Hospital of Fujian Medical UniversityQuanzhouChina
| | - Qingyan Cai
- Department of EndocrinologyThe Second Affiliated Hospital of Fujian Medical UniversityQuanzhouChina
| | - Xin Hu
- Department of EndocrinologyThe Second Affiliated Hospital of Fujian Medical UniversityQuanzhouChina
| | - Huibin Huang
- Department of EndocrinologyThe Second Affiliated Hospital of Fujian Medical UniversityQuanzhouChina
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Shumye AF, Tegegne MM, Eticha BL, Bekele MM, Woredekal AT, Asmare L. Prevalence and associated factors of proliferative diabetic retinopathy among adult diabetic patients in Northwest Ethiopia, 2023: A cross-sectional multicenter study. PLoS One 2024; 19:e0303267. [PMID: 38728350 PMCID: PMC11086827 DOI: 10.1371/journal.pone.0303267] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Accepted: 04/22/2024] [Indexed: 05/12/2024] Open
Abstract
BACKGROUND Proliferative diabetic retinopathy is one of the advanced complications of diabetic retinopathy. If left untreated, almost all eyes could lose a significant portion of their vision within four months. There is limited evidence regarding the magnitude of proliferative diabetic retinopathy and associated factors in the study setting and also in Ethiopia. PURPOSE To determine the magnitude and associated factors of proliferative diabetic retinopathy among adult diabetic patients attending Specialized Comprehensive Hospital-Diabetic Care Clinics in Northwest Ethiopia, 2023. METHODS A multicenter, hospital-based, cross-sectional study was conducted on 1219 adult diabetic patients selected by systematic random sampling technique. Data were collected through an in-person interview and physical examination. The Statistical Package for Social Science Version 20 was used to analyze the data. Logistic regression methods were used to test the association between predisposing factors and proliferative diabetic retinopathy. The adjusted odds ratio with a 95% confidence interval was used to determine the strength of association. RESULTS The prevalence of proliferative diabetic retinopathy was 3.1% (95% CI: 2.10%-4.10%). Hypertension (AOR = 4.35 (95% CI: 1.87-10.12)), peripheral neuropathy (AOR = 3.87 (95% CI: 1.57-9.54)), nephropathy (AOR = 2.58 (95% CI: 1.13-5.87)), ≥10 years duration of diabetes mellitus (AOR = 5.30 (95% CI: 2.32-12.14)), insulin use (AOR = 3.07 (95% CI: 1.08-8.68)), and poor adherence to diabetes mellitus medications (AOR = 3.77 (95% CI: 1.64-8.64)) were confirmed to have statistically significant association with proliferative diabetic retinopathy. CONCLUSION The prevalence of proliferative diabetic retinopathy among adult diabetic patients in the diabetes clinic was higher than the global study. Hypertension, peripheral neuropathy, nephropathy, ≥10 year's duration of diabetic mellitus, insulin use and poor adherence to diabetes mellitus medications were among the factors significantly associated with proliferative diabetic retinopathy.
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Affiliation(s)
- Abebech Fikade Shumye
- Department of Optometry, College of Medicine and Health Sciences, Comprehensive Specialized Hospital, University of Gondar, Gondar, Ethiopia
| | - Mebratu Mulusew Tegegne
- Department of Optometry, College of Medicine and Health Sciences, Comprehensive Specialized Hospital, University of Gondar, Gondar, Ethiopia
| | - Biruk Lelisa Eticha
- Department of Optometry, College of Medicine and Health Sciences, Comprehensive Specialized Hospital, University of Gondar, Gondar, Ethiopia
| | - Matiyas Mamo Bekele
- Department of Optometry, College of Medicine and Health Sciences, Comprehensive Specialized Hospital, University of Gondar, Gondar, Ethiopia
| | - Asamere Tsegaw Woredekal
- Department of Ophthalmology, College of Medicine and Health Sciences, Comprehensive Specialized Hospital, University of Gondar, Gondar, Ethiopia
| | - Lakew Asmare
- Department of Epidemiology and Biostatistics, College of Medicine and Health Sciences, Wollo University, Dessie, Ethiopia
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Fu X, Ren X, Chen W, Chen D. Reduced macular thickness and vascular density in abnormal glucose metabolism patients: A meta-analysis of optical coherence tomography (OCT) and OCT angiography studies. Chin Med J (Engl) 2024; 137:1054-1068. [PMID: 38563217 PMCID: PMC11062653 DOI: 10.1097/cm9.0000000000003052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Indexed: 04/04/2024] Open
Abstract
BACKGROUND Alterations in macular thickness and vascular density before clinically visible diabetic retinopathy (DR) remain inconclusive. This study aimed to determine whether retinal manifestations in abnormal glucose metabolism (AGM) patients differ from those in the healthy individuals. METHODS PubMed, Embase, and Web of Science were searched between 2000 and 2021. The eligibility criteria were AGM patients without DR. Primary and secondary outcomes measured by optical coherence tomography (OCT) and OCT angiography (OCTA) were analyzed and expressed as standardized mean differences (SMDs) with 95% confidence intervals (CIs). A random-effects model was used in the data synthesis. The potential publication bias for the variables was evaluated using Egger's test. RESULTS A total of 86 observational studies involving 13,773 participants and 15,416 eyes were included. OCT revealed that compared to healthy controls, the total macular thickness of AGM patients was thinner, including the thickness of fovea (-0.24, 95% CI [-0.39, -0.08]; P = 0.002, I2 = 87.7%), all regions of parafovea (-0.32, 95% CI [-0.54, -0.11]; P = 0.003; I2 = 71.7%) and the four quadrants of perifovea; the thickness of peripapillary retinal nerve fiber layer (pRNFL), macular retinal nerve fiber layer (mRNFL), and ganglion cell layer (GCL) also decreased. OCTA indicated that the superficial and deep vascular density decreased, the foveal avascular zone (FAZ) area enlarged, and the acircularity index (AI) reduced in AGM individuals. CONCLUSIONS Retinal thinning and microvascular lesions have occurred before the advent of clinically detectable DR; OCT and OCTA may have the potential to detect these preclinical changes. REGISTRATION PROSPERO; http://www.crd.york.ac.uk/prospero/ ; No. CRD42021269885.
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Affiliation(s)
- Xiangyu Fu
- Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
- Research Laboratory of Ophthalmology and Vision Sciences, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Xiang Ren
- Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
- Research Laboratory of Ophthalmology and Vision Sciences, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Wenyue Chen
- Department of Ophthalmology, The People’s Hospital of Guizhou Province, Guiyang, Guizhou 550002, China
| | - Danian Chen
- Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
- Research Laboratory of Ophthalmology and Vision Sciences, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
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Yang C, Yu Y, An J. Effect of High-Sucrose Diet on the Occurrence and Progression of Diabetic Retinopathy and Dietary Modification Strategies. Nutrients 2024; 16:1393. [PMID: 38732638 PMCID: PMC11085904 DOI: 10.3390/nu16091393] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2024] [Revised: 04/29/2024] [Accepted: 05/02/2024] [Indexed: 05/13/2024] Open
Abstract
As the most serious of the many worse new pathological changes caused by diabetes, there are many risk factors for the occurrence and development of diabetic retinopathy (DR). They mainly include hyperglycemia, hypertension, hyperlipidemia and so on. Among them, hyperglycemia is the most critical cause, and plays a vital role in the pathological changes of DR. High-sucrose diets (HSDs) lead to elevated blood glucose levels in vivo, which, through oxidative stress, inflammation, the production of advanced glycation end products (AGEs) and vascular endothelial growth factor (VEGF), cause plenty of pathological damages to the retina and ultimately bring about loss of vision. The existing therapies for DR primarily target the terminal stage of the disease, when irreversible visual impairment has appeared. Therefore, early prevention is particularly critical. The early prevention of DR-related vision loss requires adjustments to dietary habits, mainly by reducing sugar intake. This article primarily discusses the risk factors, pathophysiological processes and molecular mechanisms associated with the development of DR caused by HSDs. It aims to raise awareness of the crucial role of diet in the occurrence and progression of DR, promote timely changes in dietary habits, prevent vision loss and improve the quality of life. The aim is to make people aware of the importance of diet in the occurrence and progression of DR. According to the dietary modification strategies that we give, patients can change their poor eating habits in a timely manner to avoid theoretically avoidable retinopathy and obtain an excellent prognosis.
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Affiliation(s)
- Chen Yang
- State Key Laboratory of Ophthalmology, Optometry and Vision Science, Wenzhou Medical University, Wenzhou 325027, China;
- Oujiang Laboratory, Zhejiang Lab for Regenerative Medicine, Vision and Brain Health, Wenzhou 325101, China
| | - Yifei Yu
- Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing 100193, China
| | - Jianhong An
- State Key Laboratory of Ophthalmology, Optometry and Vision Science, Wenzhou Medical University, Wenzhou 325027, China;
- Oujiang Laboratory, Zhejiang Lab for Regenerative Medicine, Vision and Brain Health, Wenzhou 325101, China
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Chen T, Wang C, Zhu W, Yu F, Dong X, Su Y, Huang J, Huo L, Wan P. mm9_circ_014683 regulates microglia polarization through canonical NFκB signaling pathway in diabetic retinopathy. Cell Signal 2024; 117:111121. [PMID: 38417635 DOI: 10.1016/j.cellsig.2024.111121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2024] [Revised: 02/15/2024] [Accepted: 02/25/2024] [Indexed: 03/01/2024]
Abstract
Diabetic retinopathy (DR) is still the major cause of visual loss in working-aged people, one of the critical pathological processes are retinal microglia-mediated inflammation. Our previous study demonstrated that enhanced M1 microglial polarization was involved in retinal inflammation in DR, but the detailed mechanism needs further investigation. Circular RNAs (circRNAs) are important kind of noncoding RNAs involved in the regulation of various cell biological processes. Herein, the circRNA expression profiles of BV2 mouse microglia treated with or without glucose were detected, and a total of 347 differentially expressed circRNAs were identified in glucose-treated BV2 cells. The key circRNA mm9_circ_014683 increased after glucose stimulation. Inhibiting or overexpressing mm9_circ_014683 showed no effect on the proliferation and apoptosis of microglia. Inhibiting mm9_circ_014683 impeded M1 polarization and promoted M2 polarization, and overexpressing mm9_circ_014683 showed the opposite effect. A total of 216 differentially expressed genes were identified in mm9_circ_014683-knockdown BV2 cells, which were enriched in several signaling pathways, including the NFκB signaling pathway. Moreover, mm9_circ_014683 positively regulated the canonical, NFκB signaling pathway. Besides, mm9_circ_014683 was highly expressed in the retinal microglia of diabetic mice, and intraocular injection of Lv-circRNA inhibited M1 but enhanced M2 retinal microglial polarization. In conclusion, mm9_circ_014683 regulates microglial polarization through the canonical NFκB signaling pathway in diabetic retinopathy. This study may provide insight into the pathogenesis and treatment of DR.
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Affiliation(s)
- Tingting Chen
- Department of Ophthalmology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
| | - Congyao Wang
- Department of Ophthalmology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
| | - Wenhui Zhu
- Department of Ophthalmology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
| | - Fenfen Yu
- Department of Ophthalmology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
| | - Xia Dong
- Department of Ophthalmology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
| | - Yihua Su
- Department of Ophthalmology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
| | - Jingwen Huang
- Department of Ophthalmology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
| | - Lijun Huo
- Department of Ophthalmology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China.
| | - Pengxia Wan
- Department of Ophthalmology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China.
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Sun R, Feng J, Wang J. Underlying Mechanisms and Treatment of Cellular Senescence-Induced Biological Barrier Interruption and Related Diseases. Aging Dis 2024; 15:612-639. [PMID: 37450933 PMCID: PMC10917536 DOI: 10.14336/ad.2023.0621] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Accepted: 06/21/2023] [Indexed: 07/18/2023] Open
Abstract
Given its increasing prevalence, aging is of great concern to researchers worldwide. Cellular senescence is a physiological or pathological cellular state caused by aging and a prominent risk factor for the interruption of the integrity and functionality of human biological barriers. Health barriers play an important role in maintaining microenvironmental homeostasis within the body. The senescence of barrier cells leads to barrier dysfunction and age-related diseases. Cellular senescence has been reported to be a key target for the prevention of age-related barrier diseases, including Alzheimer's disease, Parkinson's disease, age-related macular degeneration, diabetic retinopathy, and preeclampsia. Drugs such as metformin, dasatinib, quercetin, BCL-2 inhibitors, and rapamycin have been shown to intervene in cellular senescence and age-related diseases. In this review, we conclude that cellular senescence is involved in age-related biological barrier impairment. We further outline the cellular pathways and mechanisms underlying barrier impairment caused by cellular senescence and describe age-related barrier diseases associated with senescent cells. Finally, we summarize the currently used anti-senescence pharmacological interventions and discuss their therapeutic potential for preventing age-related barrier diseases.
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Affiliation(s)
- Ruize Sun
- Department of Neurology, Shengjing Hospital, Affiliated Hospital of China Medical University, Shenyang, China
| | - Juan Feng
- Department of Neurology, Shengjing Hospital, Affiliated Hospital of China Medical University, Shenyang, China
| | - Jue Wang
- Department of Neurology, Shengjing Hospital, Affiliated Hospital of China Medical University, Shenyang, China
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Zhang M, Zhang R, Zhao X, Ma Z, Xin J, Xu S, Guo D. The role of oxidative stress in the pathogenesis of ocular diseases: an overview. Mol Biol Rep 2024; 51:454. [PMID: 38536516 DOI: 10.1007/s11033-024-09425-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2024] [Accepted: 03/07/2024] [Indexed: 02/06/2025]
Abstract
Dysregulation of oxidative stress serves as a pivotal predisposing or exacerbating factor in the intricate development of numerous pathological processes and diseases. In recent years, substantial evidence has illuminated the crucial role of reactive oxygen species (ROS) in many fundamental cellular functions, including proliferation, inflammation, apoptosis, and gene expression. Notably, producing free radicals within ROS profoundly impacts a wide range of biomolecules, such as proteins and DNA, instigating cellular damage and impairing vital cellular functions. Consequently, oxidative stress emerges as a closely intertwined factor across diverse disease spectra. Remarkably, the pathogenesis of several eye diseases, including age-related macular degeneration, glaucoma, and diabetic retinopathy, manifests an intrinsic association with oxidative stress. In this comprehensive review, we briefly summarize the recent progress in elucidating the intricate role of oxidative stress in the development of ophthalmic diseases, shedding light on potential therapeutic avenues and future research directions.
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Affiliation(s)
- Miao Zhang
- Shandong University of Traditional Chinese Medicine, Jinan, 250002, China
| | - Ruixue Zhang
- Shandong University of Traditional Chinese Medicine, Jinan, 250002, China
| | - Xiaoyue Zhao
- Shandong University of Traditional Chinese Medicine, Jinan, 250002, China
| | - Zhongyu Ma
- Shandong University of Traditional Chinese Medicine, Jinan, 250002, China
| | - Jizhao Xin
- Shandong University of Traditional Chinese Medicine, Jinan, 250002, China
| | - Shuqin Xu
- Shandong University of Traditional Chinese Medicine, Jinan, 250002, China
| | - Dadong Guo
- Medical College of Optometry and Ophthalmology, Shandong University of Traditional Chinese Medicine, Jinan, 250002, China.
- Shandong Provincial Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Therapy of Ocular Diseases, Shandong Academy of Eye Disease Prevention and Therapy, No. 48#. Yingxiongshan Road, Jinan, 250002, China.
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Yu M, Zhao S. Functional role of translocator protein and its ligands in ocular diseases (Review). Mol Med Rep 2024; 29:33. [PMID: 38186312 PMCID: PMC10804439 DOI: 10.3892/mmr.2024.13157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2023] [Accepted: 12/08/2023] [Indexed: 01/09/2024] Open
Abstract
The 18 kDa translocator protein (TSPO) is an essential outer mitochondrial membrane protein that is responsible for mitochondrial transport, maintenance of mitochondrial homeostasis and normal physiological cell function. The role of TSPO in the pathogenesis of ocular diseases is a growing area of interest. More notably, TSPO exerts positive effects in regulating various pathophysiological processes, such as the inflammatory response, oxidative stress, steroid synthesis and modulation of microglial function, in combination with a variety of specific ligands such as 1‑(2‑chlorophenyl‑N‑methylpropyl)‑3‑isoquinolinecarboxamide, 4'‑chlorodiazepam and XBD173. In the present review, the expression of TSPO in ocular tissues and the functional role of TSPO and its ligands in diverse ocular diseases was discussed.
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Affiliation(s)
- Mingyi Yu
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin 30384, P.R. China
| | - Shaozhen Zhao
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin 30384, P.R. China
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Reyes-Goya C, Santana-Garrido Á, Espinosa-Martín P, Vázquez CM, Mate A. Wild and cultivated olive trees: Nutraceutical insights of extra virgin olive oils in cardiovascular and ocular diseases. Biochim Biophys Acta Mol Basis Dis 2024; 1870:166904. [PMID: 37793462 DOI: 10.1016/j.bbadis.2023.166904] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Revised: 09/22/2023] [Accepted: 09/26/2023] [Indexed: 10/06/2023]
Abstract
Extra virgin olive oil (EVOO) from Olea europaea (cultivated olive tree) and the oil obtained from the wild olive variety or acebuche (ACE oil from Olea oleaster) contain an extraordinary number of bioactive molecules. These include oleic acid, sterols, tocopherols, triterpene compounds, and polyphenols. Both oils are known for their healthy properties and are considered to be a nutraceutical tool against cardiovascular diseases, including arterial hypertension, preeclampsia, and ocular diseases such as glaucoma or diabetic retinopathy. The benefits of EVOO and ACE oil stem from their anti-inflammatory, antioxidant, and anti-cancer properties. They also have potential as prebiotic compounds. In this update, we synthesise and illustrate the various characteristics and beneficial effects of olive oils from different varieties of olive trees, with special emphasis on Olea oleaster, also known as Olea europaea, L. var. sylvestris.
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Affiliation(s)
- C Reyes-Goya
- Departamento de Fisiología, Facultad de Farmacia, Universidad de Sevilla, 41012 Sevilla, Spain; Epidemiología Clínica y Riesgo Cardiovascular, Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío/Consejo Superior de Investigaciones Científicas/Universidad de Sevilla, 41013 Sevilla, Spain.
| | - Á Santana-Garrido
- Departamento de Fisiología, Facultad de Farmacia, Universidad de Sevilla, 41012 Sevilla, Spain; Epidemiología Clínica y Riesgo Cardiovascular, Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío/Consejo Superior de Investigaciones Científicas/Universidad de Sevilla, 41013 Sevilla, Spain
| | - P Espinosa-Martín
- Departamento de Fisiología, Facultad de Farmacia, Universidad de Sevilla, 41012 Sevilla, Spain
| | - C M Vázquez
- Departamento de Fisiología, Facultad de Farmacia, Universidad de Sevilla, 41012 Sevilla, Spain; Epidemiología Clínica y Riesgo Cardiovascular, Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío/Consejo Superior de Investigaciones Científicas/Universidad de Sevilla, 41013 Sevilla, Spain.
| | - A Mate
- Departamento de Fisiología, Facultad de Farmacia, Universidad de Sevilla, 41012 Sevilla, Spain; Epidemiología Clínica y Riesgo Cardiovascular, Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío/Consejo Superior de Investigaciones Científicas/Universidad de Sevilla, 41013 Sevilla, Spain
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