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Freitas R, Felipe S, Pacheco C, Faria E, Martins J, Fortes J, Silva D, Oliveira P, Ceccatto V. Loss of miRNA-Mediated VEGFA Regulation by SNP-Induced Impairment: A Bioinformatic Analysis in Diabetic Complications. Biomedicines 2025; 13:1192. [PMID: 40427019 PMCID: PMC12109573 DOI: 10.3390/biomedicines13051192] [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: 04/02/2025] [Revised: 05/06/2025] [Accepted: 05/08/2025] [Indexed: 05/29/2025] Open
Abstract
Background/Objectives: MicroRNAs (miRNAs) are molecules involved in biological regulation processes, including type 2 diabetes and its complications development. Single nucleotide polymorphisms (SNPs) can alter miRNA mechanisms, resulting in loss or gain effects. VEGFA is recognized for its role in angiogenesis. However, its overexpression can lead to deleterious effects, such as disorganized and inefficient vasculature. Under hyperglycemic conditions, VEGFA expression seems to increase, which may contribute to the development of microvascular and macrovascular diabetic complications. Several miRNAs are associated with VEGFA regulation and seem to act in the prevention of dysregulated expression. This study aimed to investigate SNPs in miRNA regions related to the loss effect in VEGFA regulation, examining their frequency and potential physiological effects in the development of diabetic complications. Methods: VEGFA-targeting miRNAs were identified using the R package multimiR, with validated and predicted results. Tissue expression analysis and SNP search were data-mined with Python 3 for miRNASNP-v3 SNP raw databases. Allele frequencies were obtained from dbSNP. The miRNA-mRNA interaction comparison was obtained in the miRmap tool through Python 3. MalaCards were used to infer physiological disease association. Results: The variant rs371699284 was selected in hsa-miR-654-3p among 103 potential VEGFA-targeting miRNAs. This selected SNP demonstrated promising results in bioinformatics predictions, tissue-specific expression, and population frequency, highlighting its potential role in miRNA regulation and the resulting loss in VEGFA-silencing efficiency. Conclusions: Our findings suggest that carriers of rs1238947970 may increase susceptibility to diabetic microvascular and macrovascular complications. Furthermore, in vitro and in silico studies are necessary to better understand these processes.
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Affiliation(s)
- Raquel Freitas
- Laboratory of Biochemistry and Molecular Biology of UECE—LABIEX, Superior Institute of Biomedical Science—ISCB, State University of Ceará—UECE, Silas Munguba Avenue, 1700, Fortaleza 60714-903, CE, Brazil; (S.F.); (E.F.); (J.M.); (D.S.); (P.O.); (V.C.)
| | - Stela Felipe
- Laboratory of Biochemistry and Molecular Biology of UECE—LABIEX, Superior Institute of Biomedical Science—ISCB, State University of Ceará—UECE, Silas Munguba Avenue, 1700, Fortaleza 60714-903, CE, Brazil; (S.F.); (E.F.); (J.M.); (D.S.); (P.O.); (V.C.)
| | - Christina Pacheco
- Departamento de Biologia Celular e Molecular, Federal University of Paraíba—UFPB, João Pessoa 58051-900, PB, Brazil;
| | - Emmanuelle Faria
- Laboratory of Biochemistry and Molecular Biology of UECE—LABIEX, Superior Institute of Biomedical Science—ISCB, State University of Ceará—UECE, Silas Munguba Avenue, 1700, Fortaleza 60714-903, CE, Brazil; (S.F.); (E.F.); (J.M.); (D.S.); (P.O.); (V.C.)
| | - Jonathan Martins
- Laboratory of Biochemistry and Molecular Biology of UECE—LABIEX, Superior Institute of Biomedical Science—ISCB, State University of Ceará—UECE, Silas Munguba Avenue, 1700, Fortaleza 60714-903, CE, Brazil; (S.F.); (E.F.); (J.M.); (D.S.); (P.O.); (V.C.)
| | - Jefferson Fortes
- Laboratory of Biochemistry and Molecular Biology of UECE—LABIEX, Superior Institute of Biomedical Science—ISCB, State University of Ceará—UECE, Silas Munguba Avenue, 1700, Fortaleza 60714-903, CE, Brazil; (S.F.); (E.F.); (J.M.); (D.S.); (P.O.); (V.C.)
| | - Denner Silva
- Laboratory of Biochemistry and Molecular Biology of UECE—LABIEX, Superior Institute of Biomedical Science—ISCB, State University of Ceará—UECE, Silas Munguba Avenue, 1700, Fortaleza 60714-903, CE, Brazil; (S.F.); (E.F.); (J.M.); (D.S.); (P.O.); (V.C.)
| | - Paulo Oliveira
- Laboratory of Biochemistry and Molecular Biology of UECE—LABIEX, Superior Institute of Biomedical Science—ISCB, State University of Ceará—UECE, Silas Munguba Avenue, 1700, Fortaleza 60714-903, CE, Brazil; (S.F.); (E.F.); (J.M.); (D.S.); (P.O.); (V.C.)
| | - Vania Ceccatto
- Laboratory of Biochemistry and Molecular Biology of UECE—LABIEX, Superior Institute of Biomedical Science—ISCB, State University of Ceará—UECE, Silas Munguba Avenue, 1700, Fortaleza 60714-903, CE, Brazil; (S.F.); (E.F.); (J.M.); (D.S.); (P.O.); (V.C.)
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Liao A, Fortes B, Au A, Hou K. Management of diabetic tractional retinal detachments: surgical experiences from a large tertiary academic institution. Curr Opin Ophthalmol 2025; 36:177-181. [PMID: 39950590 DOI: 10.1097/icu.0000000000001124] [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: 03/28/2025]
Abstract
PURPOSE OF REVIEW Management of diabetic tractional retinal detachments (TRDs) remains technically challenging. The purpose of this review is to provide an updated overview of current surgical techniques and important considerations when treating this condition. RECENT FINDINGS Recent advances in imaging have provided critical insights into hyaloid status and tractional forces in diabetic TRDs, greatly aiding surgical planning. Updates in vitrectomy instruments have also greatly improved anatomic success rates. However, a comprehensive preoperative evaluation and plan remains key in optimizing visual outcomes for this difficult condition. SUMMARY The surgical management of diabetic TRDs requires several key elements for successful outcomes. Timely intervention and presurgical planning are crucial, particularly in rapidly progressing cases. The use of advanced imaging and instruments enhances visualization and precision during surgery. Finally, a collaborative multispecialty approach with clear communication with patients about their prognosis is fundamental to effective care. These strategies collectively improve patient outcomes and promote visual recovery in those affected by diabetic TRDs.
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Affiliation(s)
- Albert Liao
- Retina Division, Stein Eye Institute, David Geffen School of Medicine, University of California, Los Angeles, California, USA
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Tokuc EO, Karabas L, Kanar HS, Kaplan FB, Seyyar SA, Uslubas I. Visual and anatomical outcomes of primary retinectomy for diabetic tractional retinal detachment. BMC Ophthalmol 2025; 25:216. [PMID: 40247269 PMCID: PMC12004879 DOI: 10.1186/s12886-025-04065-0] [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: 02/16/2025] [Accepted: 04/11/2025] [Indexed: 04/19/2025] Open
Abstract
PURPOSE Uncontrolled proliferative diabetic retinopathy (PDR) can cause fibrovascular growth and retinal traction, leading to tractional retinal detachment (TRD). The role of primary retinectomy in diabetic TRD remains unclear, as most studies focus on rhegmatogenous retinal detachment (RRD) with PVR. This study aims to investigate the impact of retinectomy on anatomical and visual outcomes in patients undergoing pars plana vitrectomy (PPV) for diabetic TRD. METHOD Patients who underwent primary retinectomy during PPV for diabetic TRD were retrospectively evaluated. Best corrected visual acuity (BCVA) before surgery and at the final follow-up, retinectomy characteristics, and final retinal attachment status were documented. TRD score, the quadrant and extent of the retinectomy, presence of macular displacement at final follow-up, and postoperative complications were evaluated. The relationship between the quadrants and extent of the retinectomy and visual acuity was also assessed. RESULT Thirty-eight eyes of 38 patients with mean age 60.55 ± 10.00 years were included. Mean follow-up was 23.53 ± 27.40 months. The most common locations of the retinectomy sites were extended posterior to the equator (39.5%), around the equatorial zone (34.2%), and peripheral retina (26.3%). The mean BCVA improved from 1.71 ± 0.53 logMAR to 1.48 ± 0.74 logMAR at the final follow-up. At the final visit 65.8% of patients experienced improved or maintained BCVA. Temporal retinectomy showed worse visual outcomes in the Chi-square test but not in binary logistic regression analysis. Furthermore, 26 (68.4%) eyes were attached without tamponade, 10 (26.3%) were attached under silicone oil and 2 (5.6%) remained detached under silicone oil. CONCLUSION These findings suggest that retinectomy, when deemed necessary in eyes with diabetic TRD, may not lead to poor functional and anatomical outcomes, contrary to some previous assumptions.
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Affiliation(s)
- Ecem Onder Tokuc
- Department of Ophthalmology, Kocaeli University Faculty of Medicine, Kocaeli, Turkey.
| | - Levent Karabas
- Department of Ophthalmology, Kocaeli University Faculty of Medicine, Kocaeli, Turkey
| | - Hatice Selen Kanar
- Department of Ophthalmology, Kartal Dr. Lutfi Kirdar Training and Research Hospital, Istanbul, Turkey
| | - Fatih Bilgehan Kaplan
- Department of Ophthalmology, Kirklareli Training and Research Hospital, Kirklareli, Turkey
| | - Sevim Ayça Seyyar
- Department of Ophthalmology, Gaziantep University Faculty of Medicine, Gaziantep, Turkey
| | - Isıl Uslubas
- Clinic of Ophthalmology, Kocaeli City Hospital, Kocaeli, Turkey
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Sadikan MZ, Lambuk L, Reshidan N, Ahmad Hairi H, Abd Ghapor AA, Mohamud R, Abdul Nasir NA. Molecular Mechanisms of Vitamin E in Ocular Neurodegenerative Disorders: An Update on the Emerging Evidence and Therapeutic Implications. J Ocul Pharmacol Ther 2025; 41:89-100. [PMID: 39778903 DOI: 10.1089/jop.2024.0125] [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] [Indexed: 01/11/2025] Open
Abstract
Vitamin E is renowned for its potent antioxidant properties, crucial for shielding cells against oxidative stress and damage. Deficiency in this vitamin can lead to various health issues, including neurodegenerative diseases, due to its pivotal role in preserving cell membrane integrity and combating cellular oxidative damage. While its importance for overall health, including neurodegeneration, is acknowledged, the specific correlation between vitamin E deficiency and distinct ocular neurodegenerative disorders need to be further explored. This review delves into the molecular mechanisms of vitamin E in ocular neurodegenerative disorders; diabetic retinopathy, age-related macular degeneration, glaucoma, and cataracts, and emphasising the therapeutic implications drawn from existing evidence. Relationship between vitamin E and ocular neurodegenerative disorders is widely researched on, with its primary protective mechanisms attributed to its antioxidant and anti-inflammatory properties. However, studies on the supplementation of vitamin E among human subjects present mixed results, suggesting its complexities and variability depending on factors such as the specific disorder, disease stage, genetic differences, and form of vitamin E utilized. In conclusion, while vitamin E holds promise in mitigating ocular neurodegeneration through its antioxidant and anti-inflammatory properties, its supplementation's efficacy remains nuanced and context dependent. More research works are essential to elucidate its precise role and therapeutic potential in combating various ocular neurodegenerative disorders.
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Affiliation(s)
- Muhammad Zulfiqah Sadikan
- Department of Pharmacology, Faculty of Medicine, Manipal University College Malaysia, Melaka, Malaysia
| | - Lidawani Lambuk
- Department of Immunology, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia
| | - Nurhidayah Reshidan
- School of Biology, Faculty of Applied Sciences, Universiti Teknologi MARA, Selangor, Malaysia
| | - Haryati Ahmad Hairi
- Department of Biochemistry, Faculty of Medicine, Manipal University College Malaysia, Melaka, Malaysia
| | - Afiqq Aiman Abd Ghapor
- Centre for Neuroscience Research (NeuRon), Faculty of Medicine, Universiti Teknologi MARA, Selangor, Malaysia
| | - Rohimah Mohamud
- Department of Immunology, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia
| | - Nurul Alimah Abdul Nasir
- Centre for Neuroscience Research (NeuRon), Faculty of Medicine, Universiti Teknologi MARA, Selangor, Malaysia
- Department of Medical Education, Faculty of Medicine, Universiti Teknologi MARA, Selangor, Malaysia
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Nishikiori N, Watanabe M, Higashide M, Umetsu A, Ogawa T, Furuhashi M, Ohguro H, Sato T. The Combination of PPARα Agonist GW7647 and Imeglimin Has Potent Effects on High-Glucose-Induced Cellular Biological Responses in Human Retinal Pigment Epithelium Cells. Bioengineering (Basel) 2025; 12:265. [PMID: 40150729 PMCID: PMC11939608 DOI: 10.3390/bioengineering12030265] [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: 11/01/2024] [Revised: 01/12/2025] [Accepted: 03/05/2025] [Indexed: 03/29/2025] Open
Abstract
BACKGROUND Hyperglycemic changes in the cellular biological properties of retinal pigment epithelium cells are involved in the pathophysiology of diabetic retinopathy (DR). To assess the effects of the new anti-diabetic agent imeglimin (Ime) on DR, the pharmacological effects of Ime and those of metformin (Met) in combination with the PPARα agonist GW7646 (GW) on adult retinal pigment epithelium (ARPE19) cells cultured in high-glucose conditions were compared. METHODS Cell viability, levels of reactive oxygen species (ROS), monolayer barrier function measured by transepit very much helial electrical resistance (TEER), and metabolic functions determined by an extracellular flux analyzer were evaluated. RESULTS While glucose concentrations did not alter cell viability regardless of the presence of Met or Ime, levels of ROS were significantly increased by the high-glucose conditions, and increased levels of ROS were significantly alleviated by the combination of Ime and GW but not by Met alone. Similarly, TEER values were increased by high-glucose conditions, but the effects of high-glucose conditions were dramatically enhanced by the combination of Ime and GW. Furthermore, a metabolic assay showed that an energetic shift was induced by the combination of Ime and GW, whereas energy status became quiescent with Met or Ime alone. CONCLUSIONS The collective results suggest that Ime in combination with GW has synergetic effects on high-glucose-induced cellular biological changes in ARPE19 cells.
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Affiliation(s)
- Nami Nishikiori
- Departments of Ophthalmology, Sapporo Medical University, S1W17, Chuo-ku, Sapporo 060-8556, Japan; (N.N.); (M.W.); (M.H.); (A.U.)
| | - Megumi Watanabe
- Departments of Ophthalmology, Sapporo Medical University, S1W17, Chuo-ku, Sapporo 060-8556, Japan; (N.N.); (M.W.); (M.H.); (A.U.)
| | - Megumi Higashide
- Departments of Ophthalmology, Sapporo Medical University, S1W17, Chuo-ku, Sapporo 060-8556, Japan; (N.N.); (M.W.); (M.H.); (A.U.)
| | - Araya Umetsu
- Departments of Ophthalmology, Sapporo Medical University, S1W17, Chuo-ku, Sapporo 060-8556, Japan; (N.N.); (M.W.); (M.H.); (A.U.)
| | - Toshifumi Ogawa
- Departments of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University, S1W17, Chuo-ku, Sapporo 060-8556, Japan; (T.O.); (M.F.)
- Departments of Cellular Physiology and Signal Transduction, Sapporo Medical University, S1W17, Chuo-ku, Sapporo 060-8556, Japan
| | - Masato Furuhashi
- Departments of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University, S1W17, Chuo-ku, Sapporo 060-8556, Japan; (T.O.); (M.F.)
| | - Hiroshi Ohguro
- Departments of Ophthalmology, Sapporo Medical University, S1W17, Chuo-ku, Sapporo 060-8556, Japan; (N.N.); (M.W.); (M.H.); (A.U.)
| | - Tatsuya Sato
- Departments of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University, S1W17, Chuo-ku, Sapporo 060-8556, Japan; (T.O.); (M.F.)
- Departments of Cellular Physiology and Signal Transduction, Sapporo Medical University, S1W17, Chuo-ku, Sapporo 060-8556, Japan
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Mason RH, Minaker SA, Lahaie Luna G, Bapat P, Farahvash A, Garg A, Bhambra N, Muni RH. Changes in aqueous and vitreous inflammatory cytokine levels in nonproliferative diabetic retinopathy: systematic review and meta-analysis. CANADIAN JOURNAL OF OPHTHALMOLOGY 2025; 60:e100-e116. [PMID: 39043257 DOI: 10.1016/j.jcjo.2024.05.031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/30/2022] [Revised: 11/29/2023] [Accepted: 05/27/2024] [Indexed: 07/25/2024]
Abstract
OBJECTIVE Diabetic retinopathy is a complication of diabetes mellitus with the potential for significant patient morbidity. Although changes to intraocular inflammatory cytokines are integral to disease pathogenesis, studies have been inconsistent about which exact cytokines are associated with diabetic retinopathy. We aimed to quantitatively summarize proangiogenic and proinflammatory cytokines in nonproliferative diabetic retinopathy (NPDR), given its frequency among those with diabetes mellitus. METHODS A systematic literature search without year limitation to February 21, 2022, identified 59 studies assessing vitreous or aqueous cytokine levels in NPDR, encompassing 1378 eyes with NPDR and 1288 eyes from nondiabetic controls. Effect sizes were generated as standardized mean differences (SMD) of cytokine concentrations between patients with NPDR and controls. RESULTS Concentrations (SMD, 95% confidence interval, and p value) of aqueous interleukin-6 (IL-6) (2.58, 1.17-3.99; p = 0.0003), IL-8 (1.56, 0.39-2.74; p = 0.009), IL-17 (13.55, 7.50-19.59; p < 0.001), transforming growth factor beta (TGF-β) (2.44, 1.02-3.85; p = 0.0007) and vascular endothelial growth factor (VEGF) (1.35, 0.76-1.93; p < 0.00001), and vitreous VEGF (1.49, 0.60-2.37; p = 0.001) were significantly higher in patients with NPDR when compared with those of healthy controls. CONCLUSIONS These cytokines may serve as disease markers of the biochemical alterations seen in NPDR and may guide interventions, as we move into an era of more targeted therapeutics.
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Affiliation(s)
- Ryan H Mason
- Department of Ophthalmology, St. Michael's Hospital/Unity Health Toronto, Toronto, ON; Department of Ophthalmology & Vision Sciences, University of Toronto, Toronto, ON; Kensington Vision and Research Centre, Toronto, ON
| | - Samuel A Minaker
- Department of Ophthalmology, St. Michael's Hospital/Unity Health Toronto, Toronto, ON; Department of Ophthalmology & Vision Sciences, University of Toronto, Toronto, ON; Kensington Vision and Research Centre, Toronto, ON
| | | | - Priya Bapat
- Department of Ophthalmology, St. Michael's Hospital/Unity Health Toronto, Toronto, ON; Department of Ophthalmology & Vision Sciences, University of Toronto, Toronto, ON; Kensington Vision and Research Centre, Toronto, ON
| | - Armin Farahvash
- Department of Ophthalmology, St. Michael's Hospital/Unity Health Toronto, Toronto, ON; Department of Ophthalmology & Vision Sciences, University of Toronto, Toronto, ON; Kensington Vision and Research Centre, Toronto, ON
| | - Anubhav Garg
- Department of Ophthalmology, St. Michael's Hospital/Unity Health Toronto, Toronto, ON; Department of Ophthalmology & Vision Sciences, University of Toronto, Toronto, ON; Kensington Vision and Research Centre, Toronto, ON
| | - Nishaant Bhambra
- Department of Ophthalmology, St. Michael's Hospital/Unity Health Toronto, Toronto, ON; Department of Ophthalmology & Vision Sciences, University of Toronto, Toronto, ON; Kensington Vision and Research Centre, Toronto, ON
| | - Rajeev H Muni
- Department of Ophthalmology, St. Michael's Hospital/Unity Health Toronto, Toronto, ON; Department of Ophthalmology & Vision Sciences, University of Toronto, Toronto, ON; Kensington Vision and Research Centre, Toronto, ON; University of Toronto/Kensington Health Ophthalmology Biobank and Cytokine Laboratory, Toronto, ON.
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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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Movassagh AA, Jajroudi M, Homayoun Jafari A, Khalili Pour E, Farrokhpour H, Faghihi H, Riazi H, ArabAlibeik H. Quantifying the Characteristics of Diabetic Retinopathy in Macular Optical Coherence Tomography Angiography Images: A Few-Shot Learning and Explainable Artificial Intelligence Approach. Cureus 2025; 17:e76746. [PMID: 39897224 PMCID: PMC11785394 DOI: 10.7759/cureus.76746] [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] [Accepted: 12/29/2024] [Indexed: 02/04/2025] Open
Abstract
BACKGROUND Early detection and accurate staging of diabetic retinopathy (DR) are important to prevent vision loss. Optical coherence tomography angiography (OCTA) images provide detailed insights into the retinal vasculature, revealing intricate changes that occur as DR progresses. However, interpreting these complex images requires significant expertise and is often time-intensive. Deep learning techniques have the potential to automate DR analysis. However, they typically require large datasets for effective training. To address the challenge of limited data in this emerging imaging field, a combined approach using few-shot learning (FSL) and self-attention mechanisms within explainable AI (XAI) was explored. OBJECTIVE To investigate and evaluate the potential of an FSL-self-attention XAI approach to improve the accuracy of DR staging classification using OCTA images. METHODS A total of 206 OCTA images, comprising 104 non-proliferative diabetic retinopathy (NPDR) and 102 proliferative diabetic retinopathy (PDR) cases, were analyzed using the FSL method. Three pre-trained networks (ResNet-50, DenseNet-161, and MobileNet-v2) were employed, with the top-performing model subsequently integrated with the Match-Them-Up Network (MTUNet) to provide explainable interpretations using a self-attention mechanism. The performance of the models was evaluated by applying standard metrics, including accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC-ROC). The performance of the MTUNet model is assessed by calculating pattern-matching scores for PDR and NPDR classes. RESULTS The ResNet-50 pre-trained model in FSL demonstrated the best overall performance, achieving an accuracy of 76.17%, a sensitivity of 81.83%, a specificity of 70.5%, and 0.82 AUC in classifying DR stages. MTUNet provided pattern-matching scores of 0.77 and 0.75 for PDR and NPDR classes, respectively. CONCLUSIONS FSL and self-attention mechanisms in XAI offer promising approaches for accurate DR stage classification, especially in data-limited scenarios. This could potentially facilitate early DR detection and inform clinical decision-making.
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Affiliation(s)
- Ali Akbar Movassagh
- Department of Medical Physics and Biomedical Engineering, School of Medicine, Tehran University of Medical Sciences, Tehran, IRN
| | - Mahdie Jajroudi
- Medical Informatics, Mashhad University of Medical Sciences, Mashhad, IRN
| | - Amir Homayoun Jafari
- Department of Medical Physics and Biomedical Engineering, School of Medicine, Tehran University of Medical Sciences, Tehran, IRN
| | - Elias Khalili Pour
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, IRN
| | - Hossein Farrokhpour
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, IRN
| | - Hooshang Faghihi
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, IRN
| | - Hamid Riazi
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, IRN
| | - Hossein ArabAlibeik
- Department of Medical Physics and Biomedical Engineering, School of Medicine, Tehran University of Medical Sciences, Tehran, IRN
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9
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Wei SQ, Yin P, Tang WY, Zhang ZY, Chu W, Tong Q, Li BM, Zheng WC, Wang CY. Prenatal light exposure affects diurnal rhythms and visual development of the layer embryonic retina. Poult Sci 2025; 104:104497. [PMID: 39566169 PMCID: PMC11617458 DOI: 10.1016/j.psj.2024.104497] [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: 07/24/2024] [Revised: 10/15/2024] [Accepted: 11/01/2024] [Indexed: 11/22/2024] Open
Abstract
It is believed that some wavelengths of light penetrate through eggshell and are perceived by avian embryo, and may consequently affect rhythm establishment and development. This research aimed to explore the influence of prenatal light exposure on the morphological alterations of retinal tissue, the expression of visual developmental signaling systems (TGF-β/Smad pathway), the expression of clock related genes (cClock, cBmal1, cBmal2, cAanat), and melatonin concentration in the chicken embryonic retina. Layer eggs (Jingfen No.6) were subjected to white light (5000K, WL) and green light (520 nm/515-525 nm, GL) with a 12L:12D photoperiod throughout the entire incubation period, in contrast to no light incubation (NL). The results showed that the thickness of retina and each retinal lamina of chicken embryo in WL at E20 was much thicker than that of chicken embryo in GL (P < 0.05). In contrary, the expression level of TGF-β1 mRNA and Smad2/3 protein in retina was dramatically downregulated in WL when compared to that in NL and GL (P < 0.01). Furthermore, the incubation light simultaneously significantly affected the diurnal rhythms of the chicken embryonic retina. The expression of three clock genes (cBmal1/2, cClock) and cAanat exhibited significant diurnal rhythms in GL (P < 0.05). Additionally, green light stimulation significantly enhanced melatonin secretion but did not show diurnal rhythm. However, cBmal1, cAanat, and melatonin expression exhibited diurnal rhythms (P < 0.01), while the others did not in WL. In NL, only cBmal1 exhibited diurnal rhythmicity (P < 0.01). In conclusion, providing light of different wavelengths during the incubation process of poultry can have varying effects on embryonic visual development and the establishment of diurnal rhythms. WL had an advantage to GL and NL on retina development and diurnal rhythm through significantly influencing the expression of genes related to visual developmental signaling pathways and clock genes. A well-developed retina in WL exposure chicken embryo may be beneficial for establishing a melatonin rhythm. Conversely, the established circadian rhythm could improve embryonic development.
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Affiliation(s)
- S Q Wei
- Department of Agricultural Structure and Environmental Engineering, College of Water Resources and Civil Engineering, China Agricultural University, Beijing 100083, China
| | - P Yin
- Department of Agricultural Structure and Environmental Engineering, College of Water Resources and Civil Engineering, China Agricultural University, Beijing 100083, China
| | - W Y Tang
- Department of Agricultural Structure and Environmental Engineering, College of Water Resources and Civil Engineering, China Agricultural University, Beijing 100083, China
| | - Z Y Zhang
- Department of Agricultural Structure and Environmental Engineering, College of Water Resources and Civil Engineering, China Agricultural University, Beijing 100083, China
| | - W Chu
- Department of Agricultural Structure and Environmental Engineering, College of Water Resources and Civil Engineering, China Agricultural University, Beijing 100083, China
| | - Q Tong
- Department of Agricultural Structure and Environmental Engineering, College of Water Resources and Civil Engineering, China Agricultural University, Beijing 100083, China; Key Laboratory of Agricultural Engineering in Structure and Environment Ministry of Agriculture and Rural Affairs, Beijing 100083, China; Beijing Engineering Research Center on Animal Healthy Environment, Beijing 100083, China.
| | - B M Li
- Department of Agricultural Structure and Environmental Engineering, College of Water Resources and Civil Engineering, China Agricultural University, Beijing 100083, China; Key Laboratory of Agricultural Engineering in Structure and Environment Ministry of Agriculture and Rural Affairs, Beijing 100083, China; Beijing Engineering Research Center on Animal Healthy Environment, Beijing 100083, China
| | - W C Zheng
- Department of Agricultural Structure and Environmental Engineering, College of Water Resources and Civil Engineering, China Agricultural University, Beijing 100083, China; Key Laboratory of Agricultural Engineering in Structure and Environment Ministry of Agriculture and Rural Affairs, Beijing 100083, China; Beijing Engineering Research Center on Animal Healthy Environment, Beijing 100083, China
| | - C Y Wang
- Department of Agricultural Structure and Environmental Engineering, College of Water Resources and Civil Engineering, China Agricultural University, Beijing 100083, China; Key Laboratory of Agricultural Engineering in Structure and Environment Ministry of Agriculture and Rural Affairs, Beijing 100083, China; Beijing Engineering Research Center on Animal Healthy Environment, Beijing 100083, China
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10
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Barone V, Surico PL, Cutrupi F, Mori T, Gallo Afflitto G, Di Zazzo A, Coassin M. The Role of Immune Cells and Signaling Pathways in Diabetic Eye Disease: A Comprehensive Review. Biomedicines 2024; 12:2346. [PMID: 39457658 PMCID: PMC11505591 DOI: 10.3390/biomedicines12102346] [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: 09/24/2024] [Revised: 10/02/2024] [Accepted: 10/08/2024] [Indexed: 10/28/2024] Open
Abstract
Diabetic eye disease (DED) encompasses a range of ocular complications arising from diabetes mellitus, including diabetic retinopathy, diabetic macular edema, diabetic keratopathy, diabetic cataract, and glaucoma. These conditions are leading causes of visual impairments and blindness, especially among working-age adults. Despite advancements in our understanding of DED, its underlying pathophysiological mechanisms remain incompletely understood. Chronic hyperglycemia, oxidative stress, inflammation, and neurodegeneration play central roles in the development and progression of DED, with immune-mediated processes increasingly recognized as key contributors. This review provides a comprehensive examination of the complex interactions between immune cells, inflammatory mediators, and signaling pathways implicated in the pathogenesis of DED. By delving in current research, this review aims to identify potential therapeutic targets, suggesting directions of research for future studies to address the immunopathological aspects of DED.
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Affiliation(s)
- Vincenzo Barone
- Department of Ophthalmology, Campus Bio-Medico University, 00128 Rome, Italy; (V.B.); (F.C.); (T.M.); (A.D.Z.); (M.C.)
- Ophthalmology Operative Complex Unit, Campus Bio-Medico University Hospital Foundation, 00128 Rome, Italy
| | - Pier Luigi Surico
- Department of Ophthalmology, Campus Bio-Medico University, 00128 Rome, Italy; (V.B.); (F.C.); (T.M.); (A.D.Z.); (M.C.)
- Ophthalmology Operative Complex Unit, Campus Bio-Medico University Hospital Foundation, 00128 Rome, Italy
- Schepens Eye Research Institute of Massachusetts Eye and Ear, Harvard Medical School, Boston, MA 02114, USA
| | - Francesco Cutrupi
- Department of Ophthalmology, Campus Bio-Medico University, 00128 Rome, Italy; (V.B.); (F.C.); (T.M.); (A.D.Z.); (M.C.)
- Ophthalmology Operative Complex Unit, Campus Bio-Medico University Hospital Foundation, 00128 Rome, Italy
| | - Tommaso Mori
- Department of Ophthalmology, Campus Bio-Medico University, 00128 Rome, Italy; (V.B.); (F.C.); (T.M.); (A.D.Z.); (M.C.)
- Ophthalmology Operative Complex Unit, Campus Bio-Medico University Hospital Foundation, 00128 Rome, Italy
- Department of Ophthalmology, University of California San Diego, La Jolla, CA 92122, USA
| | - Gabriele Gallo Afflitto
- Ophthalmology Unit, Department of Experimental Medicine, University of Rome “Tor Vergata”, 00128 Rome, Italy;
- Moorfields Eye Hospital NHS Foundation Trust, London EC1V 2PD, UK
| | - Antonio Di Zazzo
- Department of Ophthalmology, Campus Bio-Medico University, 00128 Rome, Italy; (V.B.); (F.C.); (T.M.); (A.D.Z.); (M.C.)
- Ophthalmology Operative Complex Unit, Campus Bio-Medico University Hospital Foundation, 00128 Rome, Italy
| | - Marco Coassin
- Department of Ophthalmology, Campus Bio-Medico University, 00128 Rome, Italy; (V.B.); (F.C.); (T.M.); (A.D.Z.); (M.C.)
- Ophthalmology Operative Complex Unit, Campus Bio-Medico University Hospital Foundation, 00128 Rome, Italy
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11
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Cammalleri M, Filippi L, Dal Monte M, Bagnoli P. A promising case of preclinical-clinical translation: β-adrenoceptor blockade from the oxygen-induced retinopathy model to retinopathy of prematurity. Front Physiol 2024; 15:1408605. [PMID: 38938747 PMCID: PMC11208707 DOI: 10.3389/fphys.2024.1408605] [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: 03/28/2024] [Accepted: 05/27/2024] [Indexed: 06/29/2024] Open
Abstract
Although compartmentalization of the eye seems to promote its experimental manipulation, drug penetration to its posterior part is severely limited by hard barriers thus hindering drug development for eye diseases. In particular, angiogenesis-related retinal diseases share common mechanisms and are responsible for the majority of cases of blindness. Their prevalence is globally increasing mostly because of the increased incidence of systemic pathologies in the adult. Despite the number of preclinical findings demonstrating the efficacy of novel treatments, therapy of retinal neovascular diseases still remains confined to intravitreal anti-vascular endothelial growth factor treatments with some extension to anti-inflammatory therapy. In the mare magnum of preclinical findings aimed to develop novel avenues for future therapies, most compounds, despite their efficacy in experimental models, do not seem to meet the criteria for their therapeutic application. In particular, the groove between preclinical findings and their clinical application increases instead of decreasing and the attempt to bridging the gap between them creates intense frustration and a sense of defeat. In this complex scenario, we will discuss here the role that overactivation of the sympathetic system plays in retinal vessel proliferation in response to hypoxia using the oxygen-induced retinopathy (OIR) model. The potential application of the beta-adrenoceptor (β-AR) blockade with propranolol to the treatment of retinopathy of prematurity will be also discussed in light of preclinical findings in the OIR model and clinical trials using propranolol in preterm infants either per os or as eye drops.
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Affiliation(s)
| | - Luca Filippi
- Neonatology Unit, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | | | - Paola Bagnoli
- Department of Biology, University of Pisa, Pisa, Italy
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12
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de Sousa BRV, Silva AS, de Assis CS, Diniz TG, Viturino MGM, de Queiroga Evangelista IW, Cavalcante-Silva LHA, Keesen TSL, de Oliveira NFP, Persuhn DC. MiR-9-3 hypermethylation is associated with stages of diabetic retinopathy. J Diabetes Metab Disord 2024; 23:1189-1198. [PMID: 38932799 PMCID: PMC11196486 DOI: 10.1007/s40200-024-01411-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2024] [Accepted: 02/20/2024] [Indexed: 06/28/2024]
Abstract
Purpose To investigate the potential relation between methylation of miR-9-3 and stages of diabetic retinopathy (DR). Additionally, we explored whether miR-9-3 methylation impacts the serum levels of Vascular Endothelial Growth Factor (VEGF). Methods A cross-sectional study was conducted with 170 participants with type 2 diabetes, including a control group (n = 64) and a diabetes retinopathy group (n = 106), which was further divided into NPDR (n = 58) and PDR (n = 48) subgroups. Epidemiological, clinical, anthropometric, biochemical ELISA assay were analysed. DNA extracted from leukocytes was used to profile miR-9-3 methylation using PCR-MSP. Results MiR-9-3 hypermethylated profile was higher in the DR group (p < 0.001) and PDR subgroup compared to DM2 control group (p < 0.001). The hypermethylated profile in the PDR subgroup was also higher compared to NPDR subgroup (p < 0.001). There was no difference between DM2 control and NPDR group (p = 0.234). Logistic regression showed that miR-9-3 hypermethylation increases the odds of presenting DR (OR: 2.826; p = 0.002) and PDR (OR: 5.472; p < 0.001). In addition, hypermethylation of miR-9-3 in the DR and NPDR subgroup was associated with higher serum VEGF-A levels (p = 0.012 and p = 0.025, respectively). Conclusion The methylation profile of the miR-9-3 promoter increases the risk of developing PDR. Higher levels of VEGF-A are associated with miR-9-3 hypermethylated profile in patients in the DR and NPDR stages. Supplementary Information The online version contains supplementary material available at 10.1007/s40200-024-01411-9.
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Affiliation(s)
| | - Alexandre Sérgio Silva
- Department of Physical Education, Federal University of Paraiba, Joao Pessoa, Paraiba, Brazil
| | - Caroline Severo de Assis
- Post-Graduate Program in Nutrition Science, Federal University of Paraiba, Joao Pessoa, Paraiba, Brazil
| | - Tainá Gomes Diniz
- Post-Graduate Program in Nutrition Science, Federal University of Paraiba, Joao Pessoa, Paraiba, Brazil
| | - Marina Gonçalves Monteiro Viturino
- Ophthalmology, Otolaryngology and Oral and Maxillofacial Surgery Unit, Lauro Wanderley University Hospital, Federal University of Paraiba, Paraiba, Brazil
| | | | | | | | | | - Darlene Camati Persuhn
- Post-Graduate Program in Nutrition Science, Federal University of Paraiba, Joao Pessoa, Paraiba, Brazil
- Department of Molecular Biology, Federal University of Paraiba, Joao Pessoa, Paraiba, Brazil
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13
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Li L, Gao J, Rao X, Liu X. Relationship between atherosclerotic cardiovascular disease and diabetic retinopathy in patients with type 2 diabetes mellitus. Medicine (Baltimore) 2024; 103:e38051. [PMID: 38728488 PMCID: PMC11081578 DOI: 10.1097/md.0000000000038051] [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: 11/15/2023] [Accepted: 04/05/2024] [Indexed: 05/12/2024] Open
Abstract
This study aimed to explore the potential correlation between atherosclerotic cardiovascular disease (ASCVD) and diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). We enrolled 6540 patients with T2DM who were receiving chronic disease management for hypertension, hyperglycemia, and hyperlipidemia in Chengyang District of Qingdao. Among them, 730 had ASCVD (ASCVD group), which 5810 did not (N-ASCVD group). The results showed significantly higher levels of age, blood glucose, glycosylated hemoglobin (HbA1c), systolic blood pressure, ASCVD family history, female proportion, and DR incidence in the N-ASCVD group. Additionally, the glomerular filtration rate was significantly lower in the ASCVD group. Logistic regression analysis revealed a positive correlation between DR and ASCVD risk. DR was further categorized into 2 subtypes, nonproliferative DR (NPDR) and proliferative DR (PDR), based on e lesion severity. Interestingly, only the PDR was associated with ASCVD. Even after accounting for traditional ASCVD risk factors such as age, sex, and family history, PDR remained associated with ASCVD, with a staggering 718% increase in the risk for patients with PDR. Therefore, there is a strong association between ASCVD and DR in individuals with T2DM, with PDR particularly exhibiting an independent and positive correlation with increased ASCVD risk.
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Affiliation(s)
- Li Li
- Endocrinology and Metabolism Department, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Jiyun Gao
- Department of Ophthalmology, Qingdao West Coast New Area District Hospital, Qingdao, Shandong, China
| | - Xiaopang Rao
- Qingdao Chengyang District People’s Hospital, Qingdao, Shandong, China
| | - Xiaoling Liu
- Pingdu City People Hospital, Qingdao, Shandong, China
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14
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Yin J, Fu X, Luo Y, Leng Y, Ao L, Xie C. A Narrative Review of Diabetic Macroangiopathy: From Molecular Mechanism to Therapeutic Approaches. Diabetes Ther 2024; 15:585-609. [PMID: 38302838 PMCID: PMC10942953 DOI: 10.1007/s13300-024-01532-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Accepted: 01/11/2024] [Indexed: 02/03/2024] Open
Abstract
Diabetic macroangiopathy, a prevalent and severe complication of diabetes mellitus, significantly contributes to the increased morbidity and mortality rates among affected individuals. This complex disorder involves multifaceted molecular mechanisms that lead to the dysfunction and damage of large blood vessels, including atherosclerosis (AS) and peripheral arterial disease. Understanding the intricate pathways underlying the development and progression of diabetic macroangiopathy is crucial for the development of effective therapeutic interventions. This review aims to shed light on the molecular mechanism implicated in the pathogenesis of diabetic macroangiopathy. We delve into the intricate interplay of chronic inflammation, oxidative stress, endothelial dysfunction, and dysregulated angiogenesis, all of which contribute to the vascular complications observed in this disorder. By exploring the molecular mechanism involved in the disease we provide insight into potential therapeutic targets and strategies. Moreover, we discuss the current therapeutic approaches used for treating diabetic macroangiopathy, including glycemic control, lipid-lowering agents, and vascular interventions.
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Affiliation(s)
- Jiacheng Yin
- Hospital of Chengdu University of Traditional Chinese Medicine No, 39 Shi-er-Qiao Road, Chengdu, 610072, Sichuan Province, People's Republic of China
| | - Xiaoxu Fu
- Hospital of Chengdu University of Traditional Chinese Medicine No, 39 Shi-er-Qiao Road, Chengdu, 610072, Sichuan Province, People's Republic of China
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, No. 39 Shi-er-Qiao Road, Chengdu, 610072, Sichuan Province, People's Republic of China
- Department of Endocrinology, Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Shi-er-Qiao Road, Chengdu, 610072, Sichuan Province, People's Republic of China
| | - Yue Luo
- Hospital of Chengdu University of Traditional Chinese Medicine No, 39 Shi-er-Qiao Road, Chengdu, 610072, Sichuan Province, People's Republic of China
| | - Yuling Leng
- Hospital of Chengdu University of Traditional Chinese Medicine No, 39 Shi-er-Qiao Road, Chengdu, 610072, Sichuan Province, People's Republic of China
| | - Lianjun Ao
- Hospital of Chengdu University of Traditional Chinese Medicine No, 39 Shi-er-Qiao Road, Chengdu, 610072, Sichuan Province, People's Republic of China
| | - Chunguang Xie
- Hospital of Chengdu University of Traditional Chinese Medicine No, 39 Shi-er-Qiao Road, Chengdu, 610072, Sichuan Province, People's Republic of China.
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, No. 39 Shi-er-Qiao Road, Chengdu, 610072, Sichuan Province, People's Republic of China.
- Department of Endocrinology, Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Shi-er-Qiao Road, Chengdu, 610072, Sichuan Province, People's Republic of China.
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15
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ALBalawi HB, Alali NM, Altemani AH, Magliyah MS, ASharari KS, ALRubayyi MS, Hashem F, Alenezi SH. Anterior segment migration of intravitreal dexamethasone implant in a patient with scleral fixation intraocular lens implant: a case report. J Surg Case Rep 2024; 2024:rjae121. [PMID: 38463741 PMCID: PMC10924725 DOI: 10.1093/jscr/rjae121] [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: 01/14/2024] [Accepted: 02/14/2024] [Indexed: 03/12/2024] Open
Abstract
Corticosteroids are crucial for treating inflammatory ocular conditions. The development of dexamethasone revolutionized targeted ocular therapy. Ozurdex, a dexamethasone implant, effectively treats various eye conditions but carries risks such as implant migration. This is a case of anterior segment migration of intravitreal dexamethasone implant, Ozurdex, in a patient with scleral fixation intraocular lens implant in whom conservative management with supine positioning and pharmacologic pupil dilation can help retain the implant back in the vitreous. Patients at high risk of Ozurdex migration should avoid its use. Educate patients on the risk of implant migration and signs of migration to present immediately to an ophthalmology emergency department to avoid corneal damage. It is essential to identify high-risk patients before considering Ozurdex migration. In some cases, conservative management can be initiated while preparing for surgical removal.
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Affiliation(s)
- Hani B ALBalawi
- Division of Ophthalmology, Department of Surgery, Faculty of Medicine, University of Tabuk, Tabuk 71491, Saudi Arabia
- Vitreoretinal Division, King Khaled Eye Specialist Hospital, Riyadh 12329, Saudi Arabia
| | - Naif M Alali
- Division of Ophthalmology, Department of Surgery, Faculty of Medicine, University of Tabuk, Tabuk 71491, Saudi Arabia
| | - Abdullah H Altemani
- Department of Family and Community Medicine, Faculty of Medicine, University of Tabuk, Tabuk 71491, Saudi Arabia
| | - Moustafa S Magliyah
- Vitreoretinal Division, King Khaled Eye Specialist Hospital, Riyadh 12329, Saudi Arabia
- Ophthalmology Department, Prince Mohammed Medical City, Aljouf 72345, Saudi Arabia
| | - Khaled S ASharari
- Vitreoretinal Division, King Khaled Eye Specialist Hospital, Riyadh 12329, Saudi Arabia
- Ophthalmology Department, Prince Mohammed Medical City, Aljouf 72345, Saudi Arabia
| | - Maram S ALRubayyi
- Radiology Department, Security Force Hospital, Riyadh 11564, Saudi Arabia
| | - Faris Hashem
- Division of Ophthalmology, Department of Surgery, Faculty of Medicine, University of Tabuk, Tabuk 71491, Saudi Arabia
| | - Saad H Alenezi
- Department of Ophthalmology, Majmaah University, Majmaah 15341, Saudi Arabia
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16
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Kulovic-Sissawo A, Tocantins C, Diniz MS, Weiss E, Steiner A, Tokic S, Madreiter-Sokolowski CT, Pereira SP, Hiden U. Mitochondrial Dysfunction in Endothelial Progenitor Cells: Unraveling Insights from Vascular Endothelial Cells. BIOLOGY 2024; 13:70. [PMID: 38392289 PMCID: PMC10886154 DOI: 10.3390/biology13020070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Revised: 01/18/2024] [Accepted: 01/19/2024] [Indexed: 02/24/2024]
Abstract
Endothelial dysfunction is associated with several lifestyle-related diseases, including cardiovascular and neurodegenerative diseases, and it contributes significantly to the global health burden. Recent research indicates a link between cardiovascular risk factors (CVRFs), excessive production of reactive oxygen species (ROS), mitochondrial impairment, and endothelial dysfunction. Circulating endothelial progenitor cells (EPCs) are recruited into the vessel wall to maintain appropriate endothelial function, repair, and angiogenesis. After attachment, EPCs differentiate into mature endothelial cells (ECs). Like ECs, EPCs are also susceptible to CVRFs, including metabolic dysfunction and chronic inflammation. Therefore, mitochondrial dysfunction of EPCs may have long-term effects on the function of the mature ECs into which EPCs differentiate, particularly in the presence of endothelial damage. However, a link between CVRFs and impaired mitochondrial function in EPCs has hardly been investigated. In this review, we aim to consolidate existing knowledge on the development of mitochondrial and endothelial dysfunction in the vascular endothelium, place it in the context of recent studies investigating the consequences of CVRFs on EPCs, and discuss the role of mitochondrial dysfunction. Thus, we aim to gain a comprehensive understanding of mechanisms involved in EPC deterioration in relation to CVRFs and address potential therapeutic interventions targeting mitochondrial health to promote endothelial function.
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Affiliation(s)
- Azra Kulovic-Sissawo
- Perinatal Research Laboratory, Department of Obstetrics and Gynaecology, Medical University of Graz, Auenbruggerplatz 14, 8036 Graz, Austria
- Research Unit Early Life Determinants (ELiD), Medical University of Graz, Auenbruggerplatz 14, 8036 Graz, Austria
| | - Carolina Tocantins
- Perinatal Research Laboratory, Department of Obstetrics and Gynaecology, Medical University of Graz, Auenbruggerplatz 14, 8036 Graz, Austria
- Research Unit Early Life Determinants (ELiD), Medical University of Graz, Auenbruggerplatz 14, 8036 Graz, Austria
- CNC-UC-Center for Neuroscience and Cell Biology, University of Coimbra, Rua Larga, 3004-504 Coimbra, Portugal
- Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-504 Coimbra, Portugal
- Doctoral Programme in Experimental Biology and Biomedicine (PDBEB), Institute for Interdisciplinary Research (IIIUC), University of Coimbra, 3004-531 Coimbra, Portugal
| | - Mariana S Diniz
- Perinatal Research Laboratory, Department of Obstetrics and Gynaecology, Medical University of Graz, Auenbruggerplatz 14, 8036 Graz, Austria
- Research Unit Early Life Determinants (ELiD), Medical University of Graz, Auenbruggerplatz 14, 8036 Graz, Austria
- CNC-UC-Center for Neuroscience and Cell Biology, University of Coimbra, Rua Larga, 3004-504 Coimbra, Portugal
- Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-504 Coimbra, Portugal
- Doctoral Programme in Experimental Biology and Biomedicine (PDBEB), Institute for Interdisciplinary Research (IIIUC), University of Coimbra, 3004-531 Coimbra, Portugal
| | - Elisa Weiss
- Perinatal Research Laboratory, Department of Obstetrics and Gynaecology, Medical University of Graz, Auenbruggerplatz 14, 8036 Graz, Austria
- Research Unit Early Life Determinants (ELiD), Medical University of Graz, Auenbruggerplatz 14, 8036 Graz, Austria
| | - Andreas Steiner
- Perinatal Research Laboratory, Department of Obstetrics and Gynaecology, Medical University of Graz, Auenbruggerplatz 14, 8036 Graz, Austria
- Research Unit Early Life Determinants (ELiD), Medical University of Graz, Auenbruggerplatz 14, 8036 Graz, Austria
| | - Silvija Tokic
- Research Unit of Analytical Mass Spectrometry, Cell Biology and Biochemistry of Inborn Errors of Metabolism, Department of Paediatrics and Adolescent Medicine, Medical University of Graz, Auenbruggerplatz 34, 8036 Graz, Austria
| | - Corina T Madreiter-Sokolowski
- Division of Molecular Biology and Biochemistry, Medical University of Graz, Neue Stiftingtalstraße 6, 8010 Graz, Austria
| | - Susana P Pereira
- CNC-UC-Center for Neuroscience and Cell Biology, University of Coimbra, Rua Larga, 3004-504 Coimbra, Portugal
- Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-504 Coimbra, Portugal
- Laboratory of Metabolism and Exercise (LaMetEx), Research Centre in Physical Activity, Health and Leisure (CIAFEL), Laboratory for Integrative and Translational Research in Population Health (ITR), Faculty of Sports, University of Porto, 4200-450 Porto, Portugal
| | - Ursula Hiden
- Perinatal Research Laboratory, Department of Obstetrics and Gynaecology, Medical University of Graz, Auenbruggerplatz 14, 8036 Graz, Austria
- Research Unit Early Life Determinants (ELiD), Medical University of Graz, Auenbruggerplatz 14, 8036 Graz, Austria
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17
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Fedoruk NA. [Current views on pathogenesis and treatment of neovascular glaucoma]. Vestn Oftalmol 2024; 140:110-116. [PMID: 38962986 DOI: 10.17116/oftalma2024140031110] [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] [Indexed: 07/05/2024]
Abstract
Neovascular glaucoma is a type of secondary glaucoma characterized by the most severe course, and ranking second among the causes of irreversible blindness. This review summarizes the results of numerous studies devoted to the search for prevention measures and the most effective treatment strategy. The main ways of preventing the development of neovascular glaucoma are timely diagnosis and elimination of ischemic processes in the retina, combined with adequate control of intraocular pressure and treatment of the underlying disease.
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Affiliation(s)
- N A Fedoruk
- Krasnov Research Institute of Eye Diseases, Moscow, Russia
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18
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Kour V, Swain J, Singh J, Singh H, Kour H. A Review on Diabetic Retinopathy. Curr Diabetes Rev 2024; 20:e201023222418. [PMID: 37867267 DOI: 10.2174/0115733998253672231011161400] [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: 03/24/2023] [Revised: 07/08/2023] [Accepted: 08/23/2023] [Indexed: 10/24/2023]
Abstract
Diabetic retinopathy is a well-recognised microvascular complication of diabetes and is among the leading cause of blindness all over the world. Over the last decade, there have been advances in the diagnosis of diabetic retinopathy and diabetic macular edema. At the same time, newer therapies for the management of diabetic retinopathy have evolved. As a result of these advances, a decline in severe vision loss due to diabetes has been witnessed in some developing countries. However, there is a steady increase in the number of people affected with diabetes, and is expected to rise further in the coming years. Therefore, it is prudent to identify diabetic retinopathy, and timely intervention is needed to decrease the burden of severe vision loss. An effort has been made to review all the existing knowledge regarding diabetic retinopathy in this article and summarize the present treatment options for diabetic retinopathy.
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Affiliation(s)
- Vijender Kour
- Consultant Ophthalmology, Department of Ophthalmology, Sub District Hospital, Tral, Pulwama, India
| | - Jayshree Swain
- Department of Endocrinology, IMS and Sum Hospital, Siksha O Anusandhan (SOA) University, Bhubaneswar, India
| | - Jaspreet Singh
- Department of Endocrinology, IMS and Sum Hospital, Siksha O Anusandhan (SOA) University, Bhubaneswar, India
| | - Hershdeep Singh
- Consultant Neurosurgeon, Department of Neurosurgery, Fortis Ludhiana, Bhubaneswar, India
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19
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Rohilla M, Rishabh, Bansal S, Garg A, Dhiman S, Dhankhar S, Saini M, Chauhan S, Alsubaie N, Batiha GES, Albezrah NKA, Singh TG. Discussing pathologic mechanisms of Diabetic retinopathy & therapeutic potentials of curcumin and β-glucogallin in the management of Diabetic retinopathy. Biomed Pharmacother 2023; 169:115881. [PMID: 37989030 DOI: 10.1016/j.biopha.2023.115881] [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: 07/30/2023] [Revised: 11/04/2023] [Accepted: 11/09/2023] [Indexed: 11/23/2023] Open
Abstract
Diabetic retinopathy (DR) is a form of retinal microangiopathy that occurs as a result of long-term Diabetes mellitus (DM). Patients with Diabetes mellitus typically suffer from DR as a progression of the disease that may be due to initiation and dysregulation of pathways like the polyol, hexosamine, the AGE/RAGE, and the PKC pathway, which all have negative impacts on eye health and vision. In this review, various databases, including PubMed, Google Scholar, Web of Science, and Science Direct, were scoured for data relevant to the aforementioned title. The three most common therapies for DR today are retinal photocoagulation, anti-vascular endothelial growth factor (VEGF) therapy, and vitrectomy, however, there are a number of drawbacks and limits to these methods. So, it is of critical importance and profound interest to discover treatments that may successfully address the pathogenesis of DR. Curcumin and β-glucogallin are the two potent compounds of natural origin that are already being used in various nutraceutical formulations for several ailments. They have been shown potent antiapoptotic, anti-inflammatory, antioxidant, anticancer, and pro-vascular function benefits in animal experiments. Their parent plant species have been used for generations by practitioners of traditional herbal medicine for the treatment and prevention of various eye ailments. In this review, we will discuss about pathophysiology of Diabetic retinopathy and the therapeutic potentials of curcumin and β-glucogallin one of the principal compounds from Curcuma longa and Emblica officinalis in Diabetic retinopathy.
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Affiliation(s)
- Manni Rohilla
- Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab 140401, India; Swami Vivekanand College of Pharmacy, Ram Nagar, Banur, Punjab 140601, India
| | - Rishabh
- M. M. College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Mullana, Ambala, Haryana 133207, India
| | - Seema Bansal
- M. M. College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Mullana, Ambala, Haryana 133207, India
| | - Anjali Garg
- Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab 140401, India; Swami Devi Dyal College of Pharmacy, Golpura Barwala, Panchkula, Haryana 134118, India
| | - Sachin Dhiman
- Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab 140401, India
| | - Sanchit Dhankhar
- Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab 140401, India
| | - Monika Saini
- Swami Vivekanand College of Pharmacy, Ram Nagar, Banur, Punjab 140601, India; M. M. College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Mullana, Ambala, Haryana 133207, India
| | - Samrat Chauhan
- Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab 140401, India.
| | - Nawal Alsubaie
- Department of Pharmacy Practice, College of Pharmacy, Princess Nourah Bint Abdulrahman University, P.O. Box 84428, Riyadh, Saudi Arabia
| | - Gaber El-Saber Batiha
- Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour 22511, AlBeheira, Egypt
| | - Nisreen Khalid Aref Albezrah
- Obstetric and Gynecology Department, Medicine College, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
| | - Thakur Gurjeet Singh
- Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab 140401, India.
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20
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Yadav M, Grezenko H, Kanukollu VMR, Rehman A, Bokhari SFH, Reza T, Franco CD, Chilla SP, Fatima H, Choudhari J, Abdullah Yahya N, Amir M, Mohsin SN. A Systematic Review of the Neuroprotective Effects of Vascular Endothelial Growth Factor (VEGF) in Diabetic Retinopathy and Diabetic Macular Edema: Unraveling the Molecular Mechanisms and Clinical Implications. Cureus 2023; 15:e51351. [PMID: 38288195 PMCID: PMC10824587 DOI: 10.7759/cureus.51351] [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] [Accepted: 12/29/2023] [Indexed: 01/31/2024] Open
Abstract
Diabetic retinopathy (DR) is a leading cause of global visual impairment, necessitating a comprehensive understanding of its vascular and neural components for effective therapeutic interventions. While vascular pathology is well-established, recent evidence suggests a neurodegenerative role in DR. Vascular endothelial growth factor (VEGF), traditionally implicated in angiogenesis, has emerged as a key player with neuroprotective potential. This systematic review evaluates the literature to shed light on molecular mechanisms and clinical implications in this regard. The review adheres to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, encompassing a thorough search strategy across multiple databases. Three in vitro studies met the inclusion criteria, highlighting the limited research in this evolving field. Findings suggest VEGF's neuroprotective effects on retinal ganglion cells (RGCs) and retinal neurons, unveiling potential therapeutic avenues. However, concerns arise regarding anti-VEGF therapies' impact on RGC survival. The review discusses the need for further research to delineate specific isoforms and signaling pathways responsible for VEGF-mediated neuroprotection. The delicate balance between angiogenesis and neuroprotection poses challenges in therapeutic development, emphasizing the importance of targeted interventions. Despite limitations, this review provides valuable insights into the intricate relationship between VEGF and neuroprotection in DR, paving the way for future investigations and redefining therapeutic strategies.
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Affiliation(s)
- Mansi Yadav
- Internal Medicine, Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences, Rohtak, IND
| | - Han Grezenko
- Translational Neuroscience, Barrow Neurological Institute, Phoenix, USA
| | | | | | | | - Taufiqa Reza
- Medicine, Avalon University School of Medicine, Youngstown, USA
| | | | - Srikar P Chilla
- Medicine, Care Hospitals, Hyderabad, IND
- Epidemiology and Public Health, School of Health Sciences, University of East London, London, GBR
| | - Hira Fatima
- Internal Medicine, Rawalpindi Medical University, Rawalpindi, PAK
| | - Jinal Choudhari
- Research and Academic Affairs, Larkin Community Hospital, Miami, USA
| | | | - Maaz Amir
- Internal Medicine, King Edward Medical University, Lahore, PAK
| | - Syed Naveed Mohsin
- Orthopedics, St James Hospital, Dublin, IRL
- General Surgery, Cavan General Hospital, Cavan, IRL
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21
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Benítez-Camacho J, Ballesteros A, Beltrán-Camacho L, Rojas-Torres M, Rosal-Vela A, Jimenez-Palomares M, Sanchez-Gomar I, Durán-Ruiz MC. Endothelial progenitor cells as biomarkers of diabetes-related cardiovascular complications. Stem Cell Res Ther 2023; 14:324. [PMID: 37950274 PMCID: PMC10636846 DOI: 10.1186/s13287-023-03537-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Accepted: 10/13/2023] [Indexed: 11/12/2023] Open
Abstract
Diabetes mellitus (DM) constitutes a chronic metabolic disease characterized by elevated levels of blood glucose which can also lead to the so-called diabetic vascular complications (DVCs), responsible for most of the morbidity, hospitalizations and death registered in these patients. Currently, different approaches to prevent or reduce DM and its DVCs have focused on reducing blood sugar levels, cholesterol management or even changes in lifestyle habits. However, even the strictest glycaemic control strategies are not always sufficient to prevent the development of DVCs, which reflects the need to identify reliable biomarkers capable of predicting further vascular complications in diabetic patients. Endothelial progenitor cells (EPCs), widely known for their potential applications in cell therapy due to their regenerative properties, may be used as differential markers in DVCs, considering that the number and functionality of these cells are affected under the pathological environments related to DM. Besides, drugs commonly used with DM patients may influence the level or behaviour of EPCs as a pleiotropic effect that could finally be decisive in the prognosis of the disease. In the current review, we have analysed the relationship between diabetes and DVCs, focusing on the potential use of EPCs as biomarkers of diabetes progression towards the development of major vascular complications. Moreover, the effects of different drugs on the number and function of EPCs have been also addressed.
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Affiliation(s)
- Josefa Benítez-Camacho
- Biomedicine, Biotechnology and Public Health Department, Science Faculty, Cádiz University, Torre Sur. Avda. República Saharaui S/N, Polígono Río San Pedro, Puerto Real, 11519, Cádiz, Spain
- Biomedical Research and Innovation Institute of Cadiz (INIBICA), Cádiz, Spain
| | - Antonio Ballesteros
- Biomedical Research and Innovation Institute of Cadiz (INIBICA), Cádiz, Spain
- Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Córdoba, Spain
| | - Lucía Beltrán-Camacho
- Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Córdoba, Spain
- Cell Biology, Physiology and Immunology Department, Córdoba University, Córdoba, Spain
| | - Marta Rojas-Torres
- Biomedicine, Biotechnology and Public Health Department, Science Faculty, Cádiz University, Torre Sur. Avda. República Saharaui S/N, Polígono Río San Pedro, Puerto Real, 11519, Cádiz, Spain
- Biomedical Research and Innovation Institute of Cadiz (INIBICA), Cádiz, Spain
| | - Antonio Rosal-Vela
- Biomedicine, Biotechnology and Public Health Department, Science Faculty, Cádiz University, Torre Sur. Avda. República Saharaui S/N, Polígono Río San Pedro, Puerto Real, 11519, Cádiz, Spain
- Biomedical Research and Innovation Institute of Cadiz (INIBICA), Cádiz, Spain
| | - Margarita Jimenez-Palomares
- Biomedicine, Biotechnology and Public Health Department, Science Faculty, Cádiz University, Torre Sur. Avda. República Saharaui S/N, Polígono Río San Pedro, Puerto Real, 11519, Cádiz, Spain
- Biomedical Research and Innovation Institute of Cadiz (INIBICA), Cádiz, Spain
| | - Ismael Sanchez-Gomar
- Biomedicine, Biotechnology and Public Health Department, Science Faculty, Cádiz University, Torre Sur. Avda. República Saharaui S/N, Polígono Río San Pedro, Puerto Real, 11519, Cádiz, Spain
- Biomedical Research and Innovation Institute of Cadiz (INIBICA), Cádiz, Spain
| | - Mª Carmen Durán-Ruiz
- Biomedicine, Biotechnology and Public Health Department, Science Faculty, Cádiz University, Torre Sur. Avda. República Saharaui S/N, Polígono Río San Pedro, Puerto Real, 11519, Cádiz, Spain.
- Biomedical Research and Innovation Institute of Cadiz (INIBICA), Cádiz, Spain.
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22
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Al-Dwairi R, El-Elimat T, Aleshawi A, Al Sharie AH, Abu Mousa BM, Al Beiruti S, Alkazaleh A, Mohidat H. Vitreous Levels of Vascular Endothelial Growth Factor and Platelet-Derived Growth Factor in Patients with Proliferative Diabetic Retinopathy: A Clinical Correlation. Biomolecules 2023; 13:1630. [PMID: 38002312 PMCID: PMC10669526 DOI: 10.3390/biom13111630] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2023] [Revised: 11/01/2023] [Accepted: 11/04/2023] [Indexed: 11/26/2023] Open
Abstract
Background: The global epidemic status of diabetic retinopathy (DR) and its burden presents an ongoing challenge to health-care systems. It is of great interest to investigate potential prognostic biomarkers of DR. Such markers could aid in detecting early stages of DR, predicting DR progression and its response to therapeutics. Herein, we investigate the prognostic value of intravitreal concentrations of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) in a DR cohort. Materials and methods: Vitreous sample acquisition was conducted at King Abdullah University Hospital (KAUH) between December 2020 and June 2022. Samples were obtained from any patient scheduled to undergo a pars plana vitrectomy (PPV) for any indication. Included patients were categorized into a DR group or a corresponding non-diabetic (ND) control group. Demographics, clinicopathological variables, standardized laboratory tests results, and optical coherence tomography (OCT) data were obtained for each included individual. Intravitreal concentrations of VEGF and PDGF were assessed using commercial enzyme-linked immunosorbent assay (ELISA). Results: A total of 80 eyes from 80 patients (DR group: n = 42 and ND control group: n = 38) were included in the analysis. The vitreous VEGF levels were significantly higher in the DR group compared to the ND control group (DR group 5744.06 ± 761.5 pg/mL versus ND control group 817.94 ± 403.1 pg/mL, p = 0.0001). In addition, the vitreous PDGF levels were also significantly higher in the DR group than those in the ND control group (DR group 4031.51 ± 410.2 pg/mL versus ND control group 2691.46 ± 821.0 pg/mL, p = 0.001). Bassline differences between test groups and clinical factors impacting VEGF and PDGF concentrations were investigated as well. Multiple regression analysis indicated PDGF as the sole independent risk factor affecting best-corrected visual acuity (BCVA) at the last follow-up visit: the higher the PDGF vitreous levels, the worst the BCVA. Conclusions: Vitreous concentrations of VEGF and PDGF are correlated with DR severity and may exhibit a possible prognostic potential value in DR. Further clinical and experimental data are warranted to confirm the observed findings and to help incorporate them into daily practice.
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Affiliation(s)
- Rami Al-Dwairi
- Division of Ophthalmology, Department of Special Surgery, Faculty of Medicine, Jordan University of Science and Technology, Irbid 22110, Jordan
| | - Tamam El-Elimat
- Department of Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid 22110, Jordan
| | - Abdelwahab Aleshawi
- Division of Ophthalmology, Department of Special Surgery, Faculty of Medicine, Jordan University of Science and Technology, Irbid 22110, Jordan
| | - Ahmed H. Al Sharie
- Department of Pathology and Microbiology, Faculty of Medicine, Jordan University of Science and Technology, Irbid 22110, Jordan
| | - Balqis M. Abu Mousa
- Department of Pathology and Microbiology, Faculty of Medicine, Jordan University of Science and Technology, Irbid 22110, Jordan
| | - Seren Al Beiruti
- Division of Ophthalmology, Department of Special Surgery, Faculty of Medicine, Jordan University of Science and Technology, Irbid 22110, Jordan
| | - Ahmad Alkazaleh
- Division of Ophthalmology, Department of Special Surgery, Faculty of Medicine, Jordan University of Science and Technology, Irbid 22110, Jordan
| | - Hasan Mohidat
- Division of Ophthalmology, Department of Special Surgery, Faculty of Medicine, Jordan University of Science and Technology, Irbid 22110, Jordan
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Sadikan MZ, Abdul Nasir NA, Lambuk L, Mohamud R, Reshidan NH, Low E, Singar SA, Mohmad Sabere AS, Iezhitsa I, Agarwal R. Diabetic retinopathy: a comprehensive update on in vivo, in vitro and ex vivo experimental models. BMC Ophthalmol 2023; 23:421. [PMID: 37858128 PMCID: PMC10588156 DOI: 10.1186/s12886-023-03155-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Accepted: 09/26/2023] [Indexed: 10/21/2023] Open
Abstract
Diabetic retinopathy (DR), one of the leading causes of visual impairment and blindness worldwide, is one of the major microvascular complications in diabetes mellitus (DM). Globally, DR prevalence among DM patients is 25%, and 6% have vision-threatening problems among them. With the higher incidence of DM globally, more DR cases are expected to be seen in the future. In order to comprehend the pathophysiological mechanism of DR in humans and discover potential novel substances for the treatment of DR, investigations are typically conducted using various experimental models. Among the experimental models, in vivo models have contributed significantly to understanding DR pathogenesis. There are several types of in vivo models for DR research, which include chemical-induced, surgical-induced, diet-induced, and genetic models. Similarly, for the in vitro models, there are several cell types that are utilised in DR research, such as retinal endothelial cells, Müller cells, and glial cells. With the advancement of DR research, it is essential to have a comprehensive update on the various experimental models utilised to mimic DR environment. This review provides the update on the in vitro, in vivo, and ex vivo models used in DR research, focusing on their features, advantages, and limitations.
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Affiliation(s)
- Muhammad Zulfiqah Sadikan
- Department of Pharmacology, Faculty of Medicine, Manipal University College Malaysia (MUCM), Bukit Baru, 75150, Melaka, Malaysia
| | - Nurul Alimah Abdul Nasir
- Centre for Neuroscience Research (NeuRon), Faculty of Medicine, Universiti Teknologi MARA, 47000, Sungai Buloh, Selangor, Malaysia.
| | - Lidawani Lambuk
- Department of Immunology, School of Medical Sciences, Universiti Sains Malaysia, 16150, Kubang Kerian, Kelantan, Malaysia
| | - Rohimah Mohamud
- Department of Immunology, School of Medical Sciences, Universiti Sains Malaysia, 16150, Kubang Kerian, Kelantan, Malaysia
| | - Nur Hidayah Reshidan
- School of Biology, Faculty of Applied Sciences, Universiti Teknologi MARA, 40450, Shah Alam, Selangor, Malaysia
| | - Evon Low
- Ageing Biology Centre, Newcastle University, NE1 7RU, Newcastle upon Tyne, UK
| | - Saiful Anuar Singar
- Department of Nutrition and Integrative Physiology, College of Health and Human Sciences, Florida State University, 32306, Tallahassee, FL, USA
| | - Awis Sukarni Mohmad Sabere
- Kulliyyah of Pharmacy, International Islamic University Malaysia, Jalan Sultan Ahmad Shah, Bandar Indera Mahkota, 25200, Kuantan, Pahang, Malaysia
| | - Igor Iezhitsa
- School of Medicine, International Medical University, 57000, Bukit Jalil, Kuala Lumpur, Malaysia
- Department of Pharmacology and Bioinformatics, Volgograd State Medical University, Pavshikh Bortsov sq. 1, 400131 , Volgograd, Russian Federation
| | - Renu Agarwal
- School of Medicine, International Medical University, 57000, Bukit Jalil, Kuala Lumpur, Malaysia
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24
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Lidder AK, Paranjpe V, Lauter AJ. Management of Neovascular Glaucoma. Int Ophthalmol Clin 2023; 63:167-183. [PMID: 37755450 DOI: 10.1097/iio.0000000000000480] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/28/2023]
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Popescu SI, Munteanu M, Patoni C, Musat AMA, Dragoescu V, Cernat CC, Popescu MN, Musat O. Role of the Vitreous in Retinal Pathology: A Narrative Review. Cureus 2023; 15:e43990. [PMID: 37622058 PMCID: PMC10446244 DOI: 10.7759/cureus.43990] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/23/2023] [Indexed: 08/26/2023] Open
Abstract
The vitreous body is an anatomically and biochemically complex structure. Because of its proximity and firm adherence to the retina, researchers have examined the link between these two structures and how their individual pathologies might be connected. Several experimental and clinical studies have already demonstrated the important role of vitreous in the pathogenesis of retinal disorders. This narrative review highlights the role of the vitreous in retinal diseases and the improvements that have been made since the introduction of optical coherence tomography. This leads to a better understanding of vitreoretinal diseases and demonstrates its determinant role in other retinal pathologies, such as diabetic retinopathy or age-related macular degeneration. As we deepen our knowledge of the vitreous's structure, function, and abnormal conditions, we can better link the changes in diseases and identify effective treatments.
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Affiliation(s)
- Stella-Ioana Popescu
- Ophthalmology, Central Military Emergency University Hospital "Dr. Carol Davila", Bucharest, ROU
- Ophthalmology, University of Medicine and Pharmacy "Victor Babeş", Timisoara, ROU
| | - Mihnea Munteanu
- Ophthalmology, University of Medicine and Pharmacy "Victor Babeş", Timisoara, ROU
| | - Cristina Patoni
- Gastroenterology, University of Medicine and Pharmacy "Carol Davila", Bucharest, ROU
- Gastroenterology, Central Military Emergency University Hospital "Dr. Carol Davila", Bucharest, ROU
| | | | - Vlad Dragoescu
- Ophthalmology, Central Military Emergency University Hospital "Dr. Carol Davila", Bucharest, ROU
| | - Corina-Cristina Cernat
- Ophthalmology, Central Military Emergency University Hospital "Dr. Carol Davila", Bucharest, ROU
| | - Marius-Nicolae Popescu
- Physical and Rehabilitation Medicine, Elias Emergency University Hospital, Bucharest, ROU
- Physical Medicine and Rehabilitation, University of Medicine and Pharmacy "Carol Davila", Bucharest, ROU
| | - Ovidiu Musat
- Ophthalmology, Central Military Emergency University Hospital "Dr. Carol Davila", Bucharest, ROU
- Ophthalmology, University of Medicine and Pharmacy "Carol Davila", Bucharest, ROU
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26
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Duong RT, Cai X, Ambati NR, Shildkrot YE. Clinical Outcomes of 27-Gauge Pars Plana Vitrectomy for Diabetic Tractional Retinal Detachment Repair. JOURNAL OF VITREORETINAL DISEASES 2023; 7:281-289. [PMID: 37927313 PMCID: PMC10621701 DOI: 10.1177/24741264231169145] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/07/2023]
Abstract
Purpose: To analyze the clinical outcomes of 27-gauge pars plana vitrectomy (PPV) repair of diabetic tractional retinal detachment (TRD) of various severities. Methods: This retrospective case series examined the outcomes of 27-gauge PPV to repair diabetic TRD from 2016 to 2020. The effect of medical and ophthalmologic history parameters and baseline detachment characteristics on visual acuity (VA) and retinal reattachment was analyzed. A grading system was established to stage the severity of the baseline vitreoretinal traction or detachment and compare the visual and anatomic outcomes between stages. Results: The study comprised 79 eyes (79 patients). The overall redetachment rate was 10.1% (8/79). The proportion of eyes with severe visual impairment (worse than 20/200) decreased from 81.0% (64/79) preoperatively to 56.9% (37/65) 6 months postoperatively (P < .001). Worse preoperative logMAR VA was associated with greater odds of redetachment (P = .017) and worse postoperative VA (P < .001). Insulin dependence was associated with better VA at 6 months (P = .017). A shorter known duration of diabetes (P = .026) and evidence of neovascularization of the iris (NVI) or angle (P = .004) were associated with worse visual outcomes. Eyes with detachment involving the posterior pole extending beyond the equator had worse VA at 6 months (P = .048). Conclusions: The primary reattachment rate after 27-gauge PPV was 89.9%. There was significant VA improvement, with a roughly 40% reduction in the number of eyes with severe visual impairment by the final follow-up. Insulin dependence, duration of diabetes, presence of NVI before surgery, and baseline posterior pole detachment extending beyond the equator were predictors of visual outcomes.
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Affiliation(s)
- Ryan T. Duong
- Department of Ophthalmology, University of Virginia, Charlottesville, VA, USA
| | - Xiaoyu Cai
- Department of Ophthalmology, University of Virginia, Charlottesville, VA, USA
| | - Naveen R. Ambati
- Department of Ophthalmology, University of Virginia, Charlottesville, VA, USA
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Zheng X, Wan J, Tan G. The mechanisms of NLRP3 inflammasome/pyroptosis activation and their role in diabetic retinopathy. Front Immunol 2023; 14:1151185. [PMID: 37180116 PMCID: PMC10167027 DOI: 10.3389/fimmu.2023.1151185] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Accepted: 04/11/2023] [Indexed: 05/15/2023] Open
Abstract
In the working-age population worldwide, diabetic retinopathy (DR), a prevalent complication of diabetes, is the main cause of vision impairment. Chronic low-grade inflammation plays an essential role in DR development. Recently, concerning the pathogenesis of DR, the Nod-Like Receptor Family Pyrin Domain Containing 3 (NLRP3) inflammasome in retinal cells has been determined as a causal factor. In the diabetic eye, the NLRP3 inflammasome is activated by several pathways (such as ROS and ATP). The activation of NPRP3 leads to the secretion of inflammatory cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18), and leads to pyroptosis, a rapid inflammatory form of lytic programmed cell death (PCD). Cells that undergo pyroptosis swell and rapture, releasing more inflammatory factors and accelerating DR progression. This review focuses on the mechanisms that activate NLRP3 inflammasome and pyroptosis leading to DR. The present research highlighted some inhibitors of NLRP3/pyroptosis pathways and novel therapeutic measures concerning DR treatment.
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Affiliation(s)
- Xiaoqin Zheng
- Department of Ophthalmology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China
| | - Jia Wan
- Department of Orthopedics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Gang Tan
- Department of Ophthalmology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China
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28
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Lee D, Hong HS. Substance P Alleviates Retinal Pigment Epithelium Dysfunction Caused by High Glucose-Induced Stress. Life (Basel) 2023; 13:life13051070. [PMID: 37240715 DOI: 10.3390/life13051070] [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: 04/10/2023] [Accepted: 04/21/2023] [Indexed: 05/28/2023] Open
Abstract
When the retina is constantly affected by high glucose (HG) due to diabetes, the barrier function of the retinal pigment epithelium (RPE) is impaired, accompanied by unnecessary vascularization. This eventually leads to the development of diabetic retinopathy (DR). This study investigated the recovery effect of substance P (SP) on RPE injured by HG. RPE was treated with HG for 24 h, and HG-induced cellular injuries were confirmed. SP was added to the dysfunctional RPE. Compared to RPE in low glucose (LG) conditions, HG-damaged RPE had large, fibrotic cell shapes, and its cellular viability decreased. HG treatment reduced tight junction protein expression levels and caused oxidative stress by interrupting the antioxidant system; this was followed by inflammatory factor intracellular adhesion molecule-1 (ICAM-1), Monocyte chemotactic protein-1 (MCP-1), and angiogenesis factor vascular endothelial growth factor (VEGF) expression. SP treatment contributed to RPE recovery by enhancing cell viability, tight junction protein expression, and RPE function under HG conditions, possibly by activating the Akt signaling pathway. Importantly, SP treatment reduced ICAM-1, MCP-1, and VEGF expression. Collectively, SP activated survival signals to suppress oxidative stress and improve retinal barrier function in RPE, accompanied by immune suppression. This suggests the possible application of SP to diabetic retinal injuries.
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Affiliation(s)
- Dahyeon Lee
- Department of Biomedical Science and Technology, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea
| | - Hyun Sook Hong
- Department of Biomedical Science and Technology, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea
- East-West Medical Research Institute, Kyung Hee University, Seoul 02447, Republic of Korea
- Kyung Hee Institute of Regenerative Medicine (KIRM), Medical Science Research Institute, Kyung Hee University Medical Center, Seoul 02447, Republic of Korea
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29
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Huang Y, Wang J, Wang Y, Kuang W, Xie M, Zhang M. Pharmacological mechanism and clinical study of Qiming granules in treating diabetic retinopathy based on network pharmacology and literature review. JOURNAL OF ETHNOPHARMACOLOGY 2023; 302:115861. [PMID: 36332761 DOI: 10.1016/j.jep.2022.115861] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Revised: 10/04/2022] [Accepted: 10/19/2022] [Indexed: 06/16/2023]
Abstract
ETHNOPHARMACOLOGY RELEVANCE Diabetic retinopathy (DR) is a general complication of diabetes, which has become a serious threat to human health worldwide. However, the best treatment is still under development. Qiming (QM) granules are mainly composed of Astragalus membranaceus, Pueraria lobata, Rehmannia Glutinosa, Lycium barbarum, Cassiae Semen, Fructus Leonuri, Pollen Typhae, and Leech, which are beneficial to qi, nourish liver and kidney, and clear collaterals and eyes. The treatment of DR is a comprehensive application based on the above traditional Chinese medicine. In recent years, satisfactory results have been achieved for DR. AIM OF THE STUDY Through the traditional application analysis, network pharmacology analysis and clinical research summary of QM granules, to review the effectiveness and advantages of QM granules in the treatment of DR comprehensively. MATERIALS AND METHODS Analysis of main active components of QM granules by network pharmacology and prediction of mechanism of action of QM granules on DR. Further, PubMed, Web of Science, and China National Knowledge Infrastructure were used to search literature, using the keywords of "Qiming granules", "diabetic retinopathy", "clinical research" and their combinations, mainly from 1999 to 2022. RESULTS Traditional pharmacological analysis, Network pharmacological analysis, animal experiments, and clinical studies have confirmed that QM granules plays a role in the treatment of DR through multiple components, multiple targets, and multiple channels. CONCLUSIONS This systematic review for the first time provides meaningful information for the further study of the pharmacodynamic material basis and pharmacological mechanism of QM granules, and also provides a basis for further study of quality markers and quality control of QM granules.
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Affiliation(s)
- Yuxia Huang
- State Key Lab Southwestern Chinese Med Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, PR China
| | - Jia Wang
- State Key Lab Southwestern Chinese Med Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, PR China
| | - Yu Wang
- State Key Lab Southwestern Chinese Med Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, PR China
| | - Wei Kuang
- State Key Lab Southwestern Chinese Med Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, PR China
| | - Mengjun Xie
- State Key Lab Southwestern Chinese Med Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, PR China.
| | - Mei Zhang
- State Key Lab Southwestern Chinese Med Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, PR China.
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Invernizzi A, Chhablani J, Viola F, Gabrielle PH, Zarranz-Ventura J, Staurenghi G. Diabetic retinopathy in the pediatric population: Pathophysiology, screening, current and future treatments. Pharmacol Res 2023; 188:106670. [PMID: 36681366 DOI: 10.1016/j.phrs.2023.106670] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Revised: 01/16/2023] [Accepted: 01/17/2023] [Indexed: 01/20/2023]
Abstract
Diabetic retinopathy (DR) is a sight threatening complication of diabetes mellitus (DM). The incidence of DR in the pediatric population has increased in the last two decades and it is expected to further rise in the future, following the increase in DM prevalence and obesity in youth. As early stages of the retinal disease are asymptomatic, screening programs are of extreme importance to guarantee a prompt diagnosis and avoid progression to more advanced, sight threatening stages. The management of DR comprises a wide range of actions starting from glycemic control, continuing with systemic and local medical treatments, up to para-surgical and surgical approaches to deal with the more aggressive complications. In this review we will describe the pathophysiology of DR trying to understand all the possible targets for currently available or future treatments. We will briefly consider the impact of screening techniques, screening strategies and their social and economic impact. Finally a large part of the review will be dedicated to medical and surgical treatments for DR including both currently available and under development therapies. Most of the available data in the literature on DR are focused on the adult population. The aim of our work is to provide clinicians and researchers with a comprehensive overview of the state of the art regarding DR in the pediatric population, considering the increasing numbers of this diseases in youth and the inevitable consequences that such a chronic disease could have if poorly managed in children.
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Affiliation(s)
- Alessandro Invernizzi
- Eye Clinic, Department of Biomedical and Clinical Science "Luigi Sacco", Luigi Sacco Hospital, University of Milan, Milan, Italy; The University of Sydney, Save Sight Institute, Discipline of Ophthalmology, Sydney Medical School, Sydney, New South Wales, Australia.
| | - Jay Chhablani
- UPMC Eye Center, University of Pittsburgh, Pittsburgh, PA, USA
| | - Francesco Viola
- Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy; Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Pierre Henry Gabrielle
- Department of Ophthalmology, University Hospital, 14 rue Paul Gaffarel, 21079 Dijon, France
| | - Javier Zarranz-Ventura
- Institut Clínic of Ophthalmology (ICOF), Hospital Clínic, Barcelona, Spain; August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain
| | - Giovanni Staurenghi
- Eye Clinic, Department of Biomedical and Clinical Science "Luigi Sacco", Luigi Sacco Hospital, University of Milan, Milan, Italy
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Tang Y, Shi Y, Fan Z. The mechanism and therapeutic strategies for neovascular glaucoma secondary to diabetic retinopathy. Front Endocrinol (Lausanne) 2023; 14:1102361. [PMID: 36755912 PMCID: PMC9900735 DOI: 10.3389/fendo.2023.1102361] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Accepted: 01/02/2023] [Indexed: 01/25/2023] Open
Abstract
Neovascular glaucoma (NVG) is a devastating secondary glaucoma characterized by the appearance of neovascular over the iris and the proliferation of fibrovascular tissue in the anterior chamber angle. Proliferative diabetic retinopathy (PDR) is one of the leading causes of NVG. Currently increasing diabetes population drive the prevalence rate of NVG into a fast-rising lane. The pathogenesis underlying NVG makes it refractory to routine management for other types of glaucoma in clinical practice. The combination of panretinal photocoagulation (PRP), anti-vascular endothelial growth factor (VEGF) injections, anti-glaucoma drugs, surgical intervention as well as blood glucose control is needed. Early diagnosis and aggressive treatment in time are crucial in halting the neovascularization process and preserving vision. This review provides an overview of NVG secondary to diabetic retinopathy (DR), including the epidemiology, pathogenesis and management, so as to provide a better understanding as well as potential therapeutic strategies for future treatment.
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Affiliation(s)
- Yizhen Tang
- Beijing Ophthalmology and Visual Sciences Key Laboratory, Department of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing, China
- Institute of Ophthalmology, Beijing Ophthalmology and Visual Sciences Key Laboratory, Capital Medical University, Beijing, China
| | - Yan Shi
- Beijing Ophthalmology and Visual Sciences Key Laboratory, Department of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing, China
- Institute of Ophthalmology, Beijing Ophthalmology and Visual Sciences Key Laboratory, Capital Medical University, Beijing, China
| | - Zhigang Fan
- Beijing Ophthalmology and Visual Sciences Key Laboratory, Department of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing, China
- Institute of Ophthalmology, Beijing Ophthalmology and Visual Sciences Key Laboratory, Capital Medical University, Beijing, China
- *Correspondence: Zhigang Fan,
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Nesper PL, Ong JX, Fawzi AA. Deep Capillary Geometric Perfusion Deficits on OCT Angiography Detect Clinically Referable Eyes with Diabetic Retinopathy. Ophthalmol Retina 2022; 6:1194-1205. [PMID: 35661804 PMCID: PMC9715815 DOI: 10.1016/j.oret.2022.05.028] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2022] [Revised: 05/25/2022] [Accepted: 05/27/2022] [Indexed: 01/06/2023]
Abstract
PURPOSE To evaluate the sensitivity (SN) and specificity (SP) of OCT angiography (OCTA) parameters for detecting clinically referable eyes with diabetic retinopathy (DR) in a cohort of patients with diabetes mellitus (DM). DESIGN Retrospective, cross-sectional study. SUBJECTS Patients with DM with various levels of DR. METHODS We measured vessel density, vessel length density (VLD), and geometric perfusion deficits (GPDs) in the full retina, superficial capillary plexus (SCP), and deep capillary plexus (DCP) on 3 × 3-mm OCTA images. Geometric perfusion deficit was recently described as retinal tissue located further than 30 μm from blood vessels, excluding the foveal avascular zone (FAZ). We modified the GPD metric by including the FAZ as an additional variable. Clinically referable eyes were defined as moderate nonproliferative DR (NPDR) or worse retinopathy, or diabetic macular edema (DME). One eye from each patient was selected for the analysis based on image quality. We used a binary logistic regression model to adjust for covariates. MAIN OUTCOME MEASURES Sensitivity, SP, and area under the curve (AUC). RESULTS Seventy-one of 150 included eyes from 150 patients (52 with DM without DR, 27 with mild NPDR, 16 with moderate NPDR, 10 with severe NPDR, 30 with proliferative DR, and 15 with DME) had clinically referable DR. Geometric perfusion deficit metric that included the FAZ performed better than GPD in detecting referable DR in the SCP (P = 0.025) but not the DCP or full retina (P > 0.05 for both). Deep capillary plexus GPD had the largest AUC for detecting clinically referable eyes (AUC = 0.965, SN = 97.2%, SP = 84.8%), which was significantly larger than the AUC for vessel density of any layer (P < 0.05 for all) but not DCP VLD (P = 0.166). The cutoff value of 2.5% for DCP GPD resulted in a highly sensitive test for detecting clinically referable eyes without adjusting for covariates (AUC = 0.955, SN = 97.2%, SP = 79.7%). CONCLUSIONS Vascular parameters in OCTA, especially in the DCP, have the potential to identify eyes that warrant further evaluation. Geometric perfusion deficits may better distinguish these clinically referable eyes with DR than standard vessel density parameters.
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Affiliation(s)
- Peter L Nesper
- Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - Janice X Ong
- Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - Amani A Fawzi
- Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
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Gao S, Zhang Y, Zhang M. Targeting Novel Regulated Cell Death: Pyroptosis, Necroptosis, and Ferroptosis in Diabetic Retinopathy. Front Cell Dev Biol 2022; 10:932886. [PMID: 35813208 PMCID: PMC9260392 DOI: 10.3389/fcell.2022.932886] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2022] [Accepted: 06/06/2022] [Indexed: 12/15/2022] Open
Abstract
Diabetic retinopathy (DR) is one of the primary causes of visual impairment in the working-age population. Retinal cell death is recognized as a prominent feature in the pathological changes of DR. Several types of cell death occurrence have been confirmed in DR, which might be the underlying mechanisms of retinal cell loss. Regulated cell death (RCD) originates from too intense or prolonged perturbations of the intracellular or extracellular microenvironment for adaptative responses to cope with stress and restore cellular homeostasis. Pyroptosis, necroptosis, and ferroptosis represent the novel discovered RCD forms, which contribute to retinal cell death in the pathogenesis of DR. This evidence provides new therapeutic targets for DR. In this review, we summarize the mechanisms of three types of RCD and analyse recent advances on the association between novel RCD and DR, aiming to provide new insights into the underlying pathogenic mechanisms and propose a potential new strategy for DR therapy.
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Affiliation(s)
- Sheng Gao
- Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, China
- Research Laboratory of Macular Disease, West China Hospital, Sichuan University, Chengdu, China
| | - Yun Zhang
- Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, China
- Research Laboratory of Macular Disease, West China Hospital, Sichuan University, Chengdu, China
| | - Meixia Zhang
- Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, China
- Research Laboratory of Macular Disease, West China Hospital, Sichuan University, Chengdu, China
- *Correspondence: Meixia Zhang,
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Gong Y, Li X, Xie L. Circ_0001897 regulates high glucose-induced angiogenesis and inflammation in retinal microvascular endothelial cells through miR-29c-3p/transforming growth factor beta 2 axis. Bioengineered 2022; 13:11694-11705. [PMID: 35510503 PMCID: PMC9275961 DOI: 10.1080/21655979.2022.2070997] [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] [Indexed: 11/22/2022] Open
Abstract
Diabetic retinopathy (DR) has become the leading cause of blindness among adults at working age. Previous studies have implicated circ_0001897 in the development of DR. In this study, we investigated the functional roles and mechanisms of circ_0001897 in high glucose-induced angiogenesis and inflammation. Peripheral blood samples from DR patients and healthy controls were collected to examine circ_0001897 expression, which demonstrated a significant upregulation of circ_0001897 in DR patients. To investigate the functional role and mechanisms of circ_0001897, human retinal microvascular endothelial cells (HRECs) were treated with high glucose (HG) to establish an in vitro DR model of endothelial cells. HG treatment induced the upregulation of circ_0001897 in HRECs, and enhanced cell proliferation, inflammatory responses, as well as in vitro angiogenesis. Circ_0001897 knockdown significantly attenuated the cell proliferation, inflammatory responses, and angiogenesis induced by HG treatment. Mechanistically, circ_0001897 sponged and inhibited the activity of mir-29c-3p, which in turn regulates the downstream target transforming growth factor beta 2 (TGFB2). The effects of circ_0001897 knockdown could be rescued by mir-29c-3p inhibitor or TGFB2 overexpression. Collectively, our data demonstrated the novel role of circ_0001897/mir-29c-3p/TGFB2 axis in regulating HG-induced inflammation and angiogenesis of HRECs. These findings suggest that targeting circ_0001897 could serve as an intervention strategy to ameliorate DR.
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Affiliation(s)
- Yudan Gong
- Department of Ophthalmology, Beilun People's Hospital, Ningbo, China
| | - Xinze Li
- Department of Traditional Chinese Medicine, Beilun People's Hospital, Ningbo, China
| | - Liuyi Xie
- Department of Ophthalmology, Beilun People's Hospital, Ningbo, China
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Rosmus DD, Lange C, Ludwig F, Ajami B, Wieghofer P. The Role of Osteopontin in Microglia Biology: Current Concepts and Future Perspectives. Biomedicines 2022; 10:biomedicines10040840. [PMID: 35453590 PMCID: PMC9027630 DOI: 10.3390/biomedicines10040840] [Citation(s) in RCA: 42] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 03/26/2022] [Accepted: 03/27/2022] [Indexed: 12/14/2022] Open
Abstract
The innate immune landscape of the central nervous system (CNS), including the brain and the retina, consists of different myeloid cell populations with distinct tasks to fulfill. Whereas the CNS borders harbor extraparenchymal CNS-associated macrophages whose main duty is to build up a defense against invading pathogens and other damaging factors from the periphery, the resident immune cells of the CNS parenchyma and the retina, microglia, are highly dynamic cells with a plethora of functions during homeostasis and disease. Therefore, microglia are constantly sensing their environment and closely interacting with surrounding cells, which is in part mediated by soluble factors. One of these factors is Osteopontin (OPN), a multifunctional protein that is produced by different cell types in the CNS, including microglia, and is upregulated in neurodegenerative and neuroinflammatory conditions. In this review, we discuss the current literature about the interaction between microglia and OPN in homeostasis and several disease entities, including multiple sclerosis (MS), Alzheimer’s and cerebrovascular diseases (AD, CVD), amyotrophic lateral sclerosis (ALS), age-related macular degeneration (AMD) and diabetic retinopathy (DR), in the context of the molecular pathways involved in OPN signaling shaping the function of microglia. As nearly all CNS diseases are characterized by pathological alterations in microglial cells, accompanied by the disturbance of the homeostatic microglia phenotype, the emergence of disease-associated microglia (DAM) states and their interplay with factors shaping the DAM-signature, such as OPN, is of great interest for therapeutical interventions in the future.
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Affiliation(s)
| | - Clemens Lange
- Eye Center, Freiburg Medical Center, University of Freiburg, 79106 Freiburg, Germany; (C.L.); (F.L.)
- Ophtha-Lab, Department of Ophthalmology, St. Franziskus Hospital, 48145 Muenster, Germany
| | - Franziska Ludwig
- Eye Center, Freiburg Medical Center, University of Freiburg, 79106 Freiburg, Germany; (C.L.); (F.L.)
| | - Bahareh Ajami
- Department of Microbiology and Immunology, Oregon Health and Science University, Portland, OR 97239, USA;
| | - Peter Wieghofer
- Institute of Anatomy, Leipzig University, 04103 Leipzig, Germany;
- Cellular Neuroanatomy, Institute of Theoretical Medicine, Medical Faculty, Augsburg University, 86159 Augsburg, Germany
- Correspondence:
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Atef MM, Shafik NM, Hafez YM, Watany MM, Selim A, Shafik HM, Safwat El-Deeb O. The evolving role of long noncoding RNA HIF1A-AS2 in diabetic retinopathy: a cross-link axis between hypoxia, oxidative stress and angiogenesis via MAPK/VEGF-dependent pathway. Redox Rep 2022; 27:70-78. [PMID: 35285425 PMCID: PMC8928809 DOI: 10.1080/13510002.2022.2050086] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
Background Diabetic retinopathy (DR) signifies a frequent serious diabetic complication influencing retinal structure and function. Dysregulation of lncRNAs drives a wide array of human diseases especially diabetes; thus, we aimed to study lncRNA HIF1A-AS2 role and its interplay with hypoxia, oxidative stress (OS), and angiogenesis in DR. Materials and methods 60 DM patients in addition to 15 healthy subjects. were enrolled. LncRNA HIF1A-AS2 mRNA relative gene expression was assessed. Hypoxia inducible factor 1-alpha (HIF-1α), vascular endothelial growth factor (VEGF), mitogen activated protein kinase (MAPK), and endoglin levels were assessed. Detection of DNA damage using comet assay, and Redox status parameters were also detected. Results LncRNA HIF1A-AS2 expression was significantly increased in diabetic patients with the highest levels in proliferative DR patients. Moreover, HIFα, VEGF, MAPK, and Endogolin levels were significantly higher in the diabetic patients compared to control group with the highest levels in in proliferative DR patients. Significant DNA damage in comet assay was observed to be the highest in this group. Conclusion We observed for the first time the imminent role of long noncoding RNA HIF1A-AS2 in DR throughout its stages and its interplay with hypoxia, OS, and angiogenesis via MAPK/VEGF-dependent pathway.
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Affiliation(s)
- Marwa Mohamed Atef
- Medical Biochemistry Department, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Noha M. Shafik
- Medical Biochemistry Department, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Yasser Mostafa Hafez
- Internal Medicine Department, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Mona Mohamed Watany
- Clinical pathology Department, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Amal Selim
- Internal Medicine Department, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Heba M. Shafik
- Ophthalmology Department, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Omnia Safwat El-Deeb
- Medical Biochemistry Department, Faculty of Medicine, Tanta University, Tanta, Egypt
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Wang S, Yu Q, Wang Y, Xu C, Niu G, Liu R. CircSLC16A12 absence inhibits high glucose-induced dysfunction in retinal microvascular endothelial cells through mediating miR-140-3p/FGF2 axis in diabetic retinopathy. Curr Eye Res 2022; 47:759-769. [PMID: 35179428 DOI: 10.1080/02713683.2022.2025845] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
BACKGROUND Diabetic retinopathy (DR) is a common microvascular complication of diabetes mellitus which can cause irreversible visual impairment and blindness. We intended to investigate the function of circular RNA (circRNA) solute carrier family 16 member 12 (SLC16A12) in DR progression. METHODS Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot assay were applied to measure RNA and protein expression. Cell apoptosis was analyzed by flow cytometry (FCM) analysis. The angiogenesis ability was assessed by tube formation assay. Enzyme-linked immunosorbent assay (ELISA) was performed to analyze the release of inflammatory cytokines. Cell oxidative stress status was evaluated using commercial kits. Dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay, and RNA-pull down assay were conducted to confirm the intermolecular interactions. RESULTS CircSLC16A12 level was enhanced in the serum samples of DR patients and high glucose (HG)-treated HRECs. CircSLC16A12 absence protected HRECs from HG-induced apoptosis, blood-retinal barrier (BRB) injury, tube formation, inflammatory response, and oxidative stress. CircSLC16A12 acted as a sponge for microRNA-140-3p (miR-140-3p), and circSLC16A12 knockdown-mediated effects were largely reversed by the absence of miR-140-3p in HRECs under HG condition. miR-140-3p interacted with the 3' untranslated region (3'UTR) of fibroblast growth factor 2 (FGF2), and the overexpression of FGF2 largely overturned miR-140-3p overexpression-mediated effects in HRECs. CircSLC16A12 interference reduced the expression of FGF2 by up-regulating miR-140-3p in HRECs. CONCLUSION CircSLC16A12 silencing suppressed HG-induced dysfunction in HRECs partly by targeting miR-140-3p/FGF2 axis.
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Affiliation(s)
- Shanshan Wang
- Department of Ophthalmic Clinic, Harbin Eye Hospital, Harbin, 150000, Heilongjiang, China
| | - Qing Yu
- Department of Eye Care, Harbin Eye Hospital, Harbin, 150000, Heilongjiang, China
| | - Yujue Wang
- Department of Ophthalmic Clinic, Harbin Eye Hospital, Harbin, 150000, Heilongjiang, China
| | - Chunyue Xu
- Department of Ophthalmic Clinic, Harbin Eye Hospital, Harbin, 150000, Heilongjiang, China
| | - Guoxiang Niu
- Department of Eye Care, Harbin Eye Hospital, Harbin, 150000, Heilongjiang, China
| | - Rui Liu
- Department of Ophthalmic Clinic, Harbin Eye Hospital, Harbin, 150000, Heilongjiang, China
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miRNA signatures in diabetic retinopathy and nephropathy: delineating underlying mechanisms. J Physiol Biochem 2022; 78:19-37. [DOI: 10.1007/s13105-021-00867-0] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2021] [Accepted: 12/15/2021] [Indexed: 12/11/2022]
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Decreased endostatin in db/db retinas is associated with optic disc intravitreal vascularization. Exp Eye Res 2021; 212:108801. [PMID: 34688624 DOI: 10.1016/j.exer.2021.108801] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Revised: 09/01/2021] [Accepted: 10/18/2021] [Indexed: 12/11/2022]
Abstract
Endostatin, a naturally cleaved fragment of type XVIII collagen with antiangiogenic activity, has been involved in the regulation of neovascularization during diabetic retinopathy. Here, the intracellular distribution of endostatin in healthy mouse and human neuroretinas has been analyzed. In addition, to study the effect of experimental hyperglycemia on retinal endostatin, the db/db mouse model has been used. Endostatin protein expression in mouse and human retinas was studied by immunofluorescence and Western blot, and compared with db/db mice. Eye fundus angiography, histology, and immunofluorescence were used to visualize mouse retinal and intravitreal vessels. For the first time, our results revealed the presence of endostatin in neurons of mouse and human retinas. Endostatin was mainly expressed in bipolar cells and photoreceptors, in contrast to the optic disc, where endostatin expression was undetectable. Diabetic mice showed a reduction of endostatin in their retinas associated with the appearance of intravitreal vessels at the optic disc in 50% of db/db mice. Intravitreal vessels showed GFAP positive neuroglia sheath, basement membrane thickening by collagen IV deposition, and presence of MMP-2 and MMP-9 in the vascular wall. All together, these results point that decreased retinal endostatin during experimental diabetes is associated with optic disc intravitreal vascularization. Based on their phenotype, these intravitreal vessels could be neovessels. However, it cannot be ruled out the possibility that they may also represent persistent hyaloid vessels.
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Santos DF, Pais M, Santos CN, Silva GA. Polyphenol Metabolite Pyrogallol- O-Sulfate Decreases Microglial Activation and VEGF in Retinal Pigment Epithelium Cells and Diabetic Mouse Retina. Int J Mol Sci 2021; 22:ijms222111402. [PMID: 34768833 PMCID: PMC8583739 DOI: 10.3390/ijms222111402] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Revised: 10/10/2021] [Accepted: 10/12/2021] [Indexed: 12/12/2022] Open
Abstract
(Poly)phenol-derived metabolites are small molecules resulting from (poly)phenol metabolization after ingestion that can be found in circulation. In the last decade, studies on the impact of (poly)phenol properties in health and cellular metabolism accumulated evidence that (poly)phenols are beneficial against human diseases. Diabetic retinopathy (DR) is characterized by inflammation and neovascularization and targeting these is of therapeutic interest. We aimed to study the effect of pyrogallol-O-sulfate (Pyr-s) metabolite in the expression of proteins involved in retinal glial activation, neovascularization, and glucose transport. The expression of PEDF, VEGF, and GLUT-1 were analyzed upon pyrogallol-O-sulfate treatment in RPE cells under high glucose and hypoxia. To test its effect on a diabetic mouse model, Ins2Akita mice were subjected to a single intraocular injection of the metabolite and the expression of PEDF, VEGF, GLUT-1, Iba1, or GFAP measured in the neural retina and/or retinal pigment epithelium (RPE), two weeks after treatment. We observed a significant decrease in the expression of pro-angiogenic VEGF in RPE cells. Moreover, pyrogallol-O-sulfate significantly decreased the expression of microglial marker Iba1 in the diabetic retina at different stages of disease progression. These results highlight the potential pyrogallol-O-sulfate metabolite as a preventive approach towards DR progression, targeting molecules involved in both inflammation and neovascularization.
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Affiliation(s)
- Daniela F. Santos
- iNOVA4HEALTH, CEDOC, NOVA Medical School, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, 1169-056 Lisboa, Portugal; (D.F.S.); (M.P.); (C.N.S.)
- ProRegeM PhD Programme—NOVA Medical School, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, 1169-056 Lisboa, Portugal
| | - Mariana Pais
- iNOVA4HEALTH, CEDOC, NOVA Medical School, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, 1169-056 Lisboa, Portugal; (D.F.S.); (M.P.); (C.N.S.)
| | - Cláudia N. Santos
- iNOVA4HEALTH, CEDOC, NOVA Medical School, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, 1169-056 Lisboa, Portugal; (D.F.S.); (M.P.); (C.N.S.)
| | - Gabriela A. Silva
- iNOVA4HEALTH, CEDOC, NOVA Medical School, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, 1169-056 Lisboa, Portugal; (D.F.S.); (M.P.); (C.N.S.)
- NOVA Medical School, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, 1169-056 Lisboa, Portugal
- Correspondence:
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Wong YH, Wong SH, Wong XT, Yi Yap Q, Yip KY, Wong LZ, Chellappan DK, Bhattamisra SK, Candasamy M. Genetic associated complications of type 2 Diabetes Mellitus: a review. Panminerva Med 2021; 64:274-288. [PMID: 34609116 DOI: 10.23736/s0031-0808.21.04285-3] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
According to the International Diabetes Federation, the number of adults (age of 20-79) being diagnosed with Diabetes Mellitus (DM) have increased from 285 million in year 2009 to 463 million in year 2019 which comprises of 95% Type 2 DM patient (T2DM). Research have claimed that genetic predisposition could be one of the factors causing T2DM complications. In addition, T2DMcomplications cause an incremental risk to mortality. Therefore, this article aims to discuss some complications of T2DM in and their genetic association. The complications that are discussed in this article are diabetic nephropathy, diabetes induced cardiovascular disease, diabetic neuropathy, Diabetic Foot Ulcer (DFU) and Alzheimer's disease. According to the information obtained, genes associated with diabetic nephropathy (DN) are gene GABRR1 and ELMO1 that cause injury to glomerular. Replication of genes FRMD3, CARS and MYO16/IRS2 shown to have link with DN. The increase of gene THBS2, NGAL, PIP, TRAF6 polymorphism, ICAM-1 encoded for rs5498 polymorphism and C667T increase susceptibility towards DN in T2DM patient. Genes associated with cardiovascular diseases are Adiponectin gene (ACRP30) and Apolipoprotein E (APOE) polymorphism gene with ξ2 allele. Haptoglobin (Hp) 1-1 genotype and Mitochondria Superoxide Dismutase 2 (SOD2) plays a role in cardiovascular events. As for genes related to diabetic neuropathy, Janus Kinase (JAK), mutation of SCN9A and TRPA1 gene and destruction of miRNA contribute to pathogenesis of diabetic neuropathy among T2DM patients. Expression of cytokine IL-6, IL-10, miR-146a are found to cause diabetic neuropathy. Besides, A1a16Va1 gene polymorphism, an oxidative stress influence was found as one of the gene factors. Diabetic retinopathy (DR) is believed to have association with Monocyte Chemoattractant Protein-1 (MCP-1) and Insulin-like Growth Factor 1 (IGF1). Over-expression of gene ENPP1, IL-6 pro-inflammatory cytokine, ARHGAP22's protein rs3844492 polymorphism and TLR4 heterozygous genotype are contributing to significant pathophysiological process causing DR, while research found increases level of UCP1 gene protects retina cells from oxidative stress. Diabetic Foot Ulcer (DFU) is manifested by slowing in reepithelialisation of keratinocyte, persistence wound inflammation and healing impairment. Reepithelialisation disturbance was caused by E2F3 gene, reduction of Tacl gene encoded substance P causing persistence inflammation while expression of MMp-9 polymorphism contributes to healing impairment. A decrease in HIF-1a gene expression leads to increased risk of pathogenesis, while downregulation of TLR2 increases severity of wound in DFU patients. SNPs alleles has been shown to have significant association between the genetic dispositions of T2DM and Alzheimer's disease (AD). The progression of AD can be due to the change in DNA methylation of CLOCK gene, followed with worsening of AD by APOE4 gene due to dyslipidaemia condition in T2DM patients. Insulin resistance is also a factor that contributes to pathogenesis of AD.
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Affiliation(s)
- Yee H Wong
- School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia
| | - Shen H Wong
- School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia
| | - Xiao T Wong
- School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia
| | - Qiao Yi Yap
- School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia
| | - Khar Y Yip
- School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia
| | - Liang Z Wong
- School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia
| | - Dinesh K Chellappan
- Department of Life Sciences, School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia
| | - Subrat K Bhattamisra
- Department of Life Sciences, School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia
| | - Mayuren Candasamy
- Department of Life Sciences, School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia -
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Shi Q, Tang J, Wang M, Xu L, Shi L. Knockdown of Long Non-coding RNA TUG1 Suppresses Migration and Tube Formation in High Glucose-Stimulated Human Retinal Microvascular Endothelial Cells by Sponging miRNA-145. Mol Biotechnol 2021; 64:171-177. [PMID: 34554391 DOI: 10.1007/s12033-021-00398-5] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2021] [Accepted: 09/13/2021] [Indexed: 11/29/2022]
Abstract
Diabetic retinopathy (DR) is a serious complication of diabetes mellitus. The purpose of this study was to investigate the potential functional role of long non-coding RNA TUG1 in high glucose (HG)-stimulated human retinal microvascular endothelial cells (hRMECs). The results demonstrated that following 72 h of HG stimulation, enhanced proliferation, migration, and tube formation process were observed in hRMECs. Moreover, HG treatment markedly increased TUG1 expression in hRMECs, and knockdown of TUG1 notably restrained the aberrant phenotypes of hRMECs induced by HG. Mechanistically, TUG1 may serve as a competing endogenous RNA (ceRNA) for miR-145, thereby blocking the repression on VEGF-A in hRMECs. Rescue experiments further indicated that inhibition of miR-145 abolished the beneficial role of TUG1 knockdown in HG-treated hRMECs. Our data suggested that knockdown of TUG1 protects hRMECs against HG stimulation partly by regulating miR-145/VEGF-A axis.
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Affiliation(s)
- Qian Shi
- Department of Ophthalmology, Yixing Eye Hospital, Intersection of Hongta Road Kang Ming Road, Yicheng Street, Yixing, 214200, Jiangsu, China.
| | - Jinhua Tang
- Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Minfeng Wang
- Department of Ophthalmology, Yixing Eye Hospital, Intersection of Hongta Road Kang Ming Road, Yicheng Street, Yixing, 214200, Jiangsu, China
| | - Lishuai Xu
- Department of Ophthalmology and Optometry, North Sichuan Medical College, Nanchong, 637000, Sichuan, China.,Department of Ophthalmology, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, Sichuan, China
| | - Lijun Shi
- Department of Ophthalmology, Yixing Eye Hospital, Intersection of Hongta Road Kang Ming Road, Yicheng Street, Yixing, 214200, Jiangsu, China
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Hsiao CC, Chang YC, Hsiao YT, Chen PH, Hsieh MC, Wu WC, Kao YH. Triamcinolone acetonide modulates TGF‑β2‑induced angiogenic and tissue‑remodeling effects in cultured human retinal pigment epithelial cells. Mol Med Rep 2021; 24:802. [PMID: 34523693 PMCID: PMC8456346 DOI: 10.3892/mmr.2021.12442] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Accepted: 08/31/2021] [Indexed: 12/17/2022] Open
Abstract
Transforming growth factor-β2 (TGF-β2) has been implicated in the pathogenesis of proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR), due to its ability to stimulate the overproduction of pro-angiogenic factors, such as vascular endothelial growth factor (VEGF), and remodeling of the extracellular matrix (ECM). Although intravitreal triamcinolone acetonide (TA) is clinically useful in the treatment of PVR and PDR, its molecular mechanism has yet to be fully elucidated. The present study investigated whether TA treatment altered TGF-β2-driven biological effects on the behavior of cultured human retinal pigment epithelial (RPE) cells, in order to determine which signaling pathway may be essential for the pharmacological action of TA. The R-50 human RPE cell line was treated with TA in the presence of TGF-β2, followed by analyses of cell viability and contraction using cell viability and collagen gel contraction assays. VEGF mRNA expression and protein production were measured using reverse transcription-quantitative PCR and ELISA, respectively. The phosphorylation status of signaling mediators and the protein expression of type I collagen (COL1A1), α-smooth muscle actin (α-SMA), and ECM-remodeling enzymes, including MMP-2 and MMP-9, were analyzed using western blotting. The gelatinolytic activity of MMPs was detected using gelatin zymography. TA treatment exhibited no prominent cytotoxicity but markedly antagonized TGF-β2-induced cytostatic effects on RPE cell viability and TGF-β2-enhanced contractility in collagen gels. In the context of TGF-β2-related signaling, TA significantly attenuated TGF-β2-elicited Smad2, extracellular-regulated kinase (ERK)1/2 and p38 mitogen-activated protein kinase (MAPK) phosphorylation. Moreover, TA markedly mitigated TGF-β2-induced VEGF upregulation through ablation of p38 signaling activity. TA also partially attenuated TGF-β2-elicted expression of COL1A1, α-SMA, MMP-2, and MMP-9, but only suppressed TGF-β2-induced MMP-9 gelatinolytic activity. Mechanistically, the MEK/ERK signaling pathway may have a critical role in the TGF-β2-induced upregulation of COL1A1, α-SMA and MMP-9. In conclusion, TA may be considered a useful therapeutic agent for treating TGF-β2-associated intraocular angiogenesis and tissue remodeling, the underlying mechanism of which may involve the ERK and p38 MAPK signaling pathways.
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Affiliation(s)
- Chih-Cheng Hsiao
- Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan, R.O.C
| | - Yo-Chen Chang
- Department of Ophthalmology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan, R.O.C
| | - Yu-Ting Hsiao
- Department of Ophthalmology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan, R.O.C
| | - Po-Han Chen
- Department of Medical Research, E‑Da Hospital, Kaohsiung 82445, Taiwan, R.O.C
| | - Ming-Chu Hsieh
- Department of Ophthalmology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80761, Taiwan, R.O.C
| | - Wen-Chuan Wu
- Department of Ophthalmology, China Medical University Hospital, Taichung 404332, Taiwan, R.O.C
| | - Ying-Hsien Kao
- Department of Medical Research, E‑Da Hospital, Kaohsiung 82445, Taiwan, R.O.C
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Simó R, Simó-Servat O, Bogdanov P, Hernández C. Neurovascular Unit: A New Target for Treating Early Stages of Diabetic Retinopathy. Pharmaceutics 2021; 13:pharmaceutics13081320. [PMID: 34452281 PMCID: PMC8399715 DOI: 10.3390/pharmaceutics13081320] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Revised: 08/18/2021] [Accepted: 08/19/2021] [Indexed: 01/02/2023] Open
Abstract
The concept of diabetic retinopathy as a microvascular disease has evolved and is now considered a more complex diabetic complication in which neurovascular unit impairment plays an essential role and, therefore, can be considered as a main therapeutic target in the early stages of the disease. However, neurodegeneration is not always the apparent primary event in the natural story of diabetic retinopathy, and a phenotyping characterization is recommendable to identify those patients in whom neuroprotective treatment might be of benefit. In recent years, a myriad of treatments based on neuroprotection have been tested in experimental models, but more interestingly, there are drugs with a dual activity (neuroprotective and vasculotropic). In this review, the recent evidence concerning the therapeutic approaches targeting neurovascular unit impairment will be presented, along with a critical review of the scientific gaps and problems which remain to be overcome before our knowledge can be transferred to clinical practice.
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Affiliation(s)
- Rafael Simó
- Diabetes and Metabolism Research Unit, Vall d’Hebron Research Institute (VHIR), 08035 Barcelona, Spain; (O.S.-S.); (P.B.); (C.H.)
- Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ICSIII), 28029 Madrid, Spain
- Correspondence:
| | - Olga Simó-Servat
- Diabetes and Metabolism Research Unit, Vall d’Hebron Research Institute (VHIR), 08035 Barcelona, Spain; (O.S.-S.); (P.B.); (C.H.)
- Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ICSIII), 28029 Madrid, Spain
| | - Patricia Bogdanov
- Diabetes and Metabolism Research Unit, Vall d’Hebron Research Institute (VHIR), 08035 Barcelona, Spain; (O.S.-S.); (P.B.); (C.H.)
- Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ICSIII), 28029 Madrid, Spain
| | - Cristina Hernández
- Diabetes and Metabolism Research Unit, Vall d’Hebron Research Institute (VHIR), 08035 Barcelona, Spain; (O.S.-S.); (P.B.); (C.H.)
- Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ICSIII), 28029 Madrid, Spain
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Durante W, Behnammanesh G, Peyton KJ. Effects of Sodium-Glucose Co-Transporter 2 Inhibitors on Vascular Cell Function and Arterial Remodeling. Int J Mol Sci 2021; 22:ijms22168786. [PMID: 34445519 PMCID: PMC8396183 DOI: 10.3390/ijms22168786] [Citation(s) in RCA: 68] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Revised: 08/10/2021] [Accepted: 08/11/2021] [Indexed: 12/20/2022] Open
Abstract
Cardiovascular disease is the leading cause of morbidity and mortality in diabetes. Recent clinical studies indicate that sodium-glucose co-transporter 2 (SGLT2) inhibitors improve cardiovascular outcomes in patients with diabetes. The mechanism underlying the beneficial effect of SGLT2 inhibitors is not completely clear but may involve direct actions on vascular cells. SGLT2 inhibitors increase the bioavailability of endothelium-derived nitric oxide and thereby restore endothelium-dependent vasodilation in diabetes. In addition, SGLT2 inhibitors favorably regulate the proliferation, migration, differentiation, survival, and senescence of endothelial cells (ECs). Moreover, they exert potent antioxidant and anti-inflammatory effects in ECs. SGLT2 inhibitors also inhibit the contraction of vascular smooth muscle cells and block the proliferation and migration of these cells. Furthermore, studies demonstrate that SGLT2 inhibitors prevent postangioplasty restenosis, maladaptive remodeling of the vasculature in pulmonary arterial hypertension, the formation of abdominal aortic aneurysms, and the acceleration of arterial stiffness in diabetes. However, the role of SGLT2 in mediating the vascular actions of these drugs remains to be established as important off-target effects of SGLT2 inhibitors have been identified. Future studies distinguishing drug- versus class-specific effects may optimize the selection of specific SGLT2 inhibitors in patients with distinct cardiovascular pathologies.
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Sun Y, Ni Y, Kong N, Huang C. TLR2 signaling contributes to the angiogenesis of oxygen-induced retinopathy. Exp Eye Res 2021; 210:108716. [PMID: 34352266 DOI: 10.1016/j.exer.2021.108716] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Revised: 07/05/2021] [Accepted: 07/30/2021] [Indexed: 11/15/2022]
Abstract
PURPOSE To evaluate the role of Toll-like receptor 2 (TLR2) signaling in retinal neovascularization in a mouse model of oxygen-induced retinopathy (OIR). MATERIALS AND METHODS The OIR model was established in C57BL/6J wild type (WT) mice and TLR2-/- mice. Retinal neovascularization in the OIR model was measured by counting new vascular cell nuclei above the internal limiting membrane and analyzing flat-mounted retinas perfused with fluorescein dextran and immunostained with Griffonia Simplicifolia (GS) isolectin. The expression of TLR2 and VEGF in the retina was detected by immunofluorescence. Expression of TGF- β1, b-FGF, and IL-6 mRNA in the retina was measured by quantitative real-time PCR. RESULTS Compared to WT OIR mice, retinal neovascularization was attenuated in TLR2-/- OIR mice. The co-expressions of TLR2 and VEGF were remarkably and consistently increased in WT OIR mice; however, there was no expression of TLR2 and a significant decrease in VEGF expression in TLR2-/- OIR mice. These results suggest that TLR2 plays a central role in OIR model angiogenesis. Expression of TGF- β1, b-FGF, and IL-6 mRNA were reduced in the TLR2-/- OIR mice, suggesting that the inflammatory response induced by TLR2 relates to angiogenesis. CONCLUSION TLR2 signaling in the retina is associated with neovascularization in mice. Inflammation contributes to the activation of angiogenesis and is partially mediated through the TLR2-VEGF retinal signaling pathway.
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Affiliation(s)
- Yuying Sun
- State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong Province, China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong Province, China; Department of Cancer Prevention, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong Province, China
| | - Yao Ni
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 510060, Guangdong Province, China
| | - Ning Kong
- Department of Ophthalmology, Panyu Central Hospital, Guangzhou, 510080, Guangdong Province, China.
| | - Chunyu Huang
- State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong Province, China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong Province, China; Department of Endoscopy, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong Province, China.
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Diabetic retinopathy and diabetic macular oedema pathways and management: UK Consensus Working Group. Eye (Lond) 2021; 34:1-51. [PMID: 32504038 DOI: 10.1038/s41433-020-0961-6] [Citation(s) in RCA: 100] [Impact Index Per Article: 25.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
The management of diabetic retinopathy (DR) has evolved considerably over the past decade, with the availability of new technologies (diagnostic and therapeutic). As such, the existing Royal College of Ophthalmologists DR Guidelines (2013) are outdated, and to the best of our knowledge are not under revision at present. Furthermore, there are no other UK guidelines covering all available treatments, and there seems to be significant variation around the UK in the management of diabetic macular oedema (DMO). This manuscript provides a summary of reviews the pathogenesis of DR and DMO, including role of vascular endothelial growth factor (VEGF) and non-VEGF cytokines, clinical grading/classification of DMO vis a vis current terminology (of centre-involving [CI-DMO], or non-centre involving [nCI-DMO], systemic risks and their management). The excellent UK DR Screening (DRS) service has continued to evolve and remains world-leading. However, challenges remain, as there are significant variations in equipment used, and reproducible standards of DMO screening nationally. The interphase between DRS and the hospital eye service can only be strengthened with further improvements. The role of modern technology including optical coherence tomography (OCT) and wide-field imaging, and working practices including virtual clinics and their potential in increasing clinic capacity and improving patient experiences and outcomes are discussed. Similarly, potential roles of home monitoring in diabetic eyes in the future are explored. The role of pharmacological (intravitreal injections [IVT] of anti-VEGFs and steroids) and laser therapies are summarised. Generally, IVT anti-VEGF are offered as first line pharmacologic therapy. As requirements of diabetic patients in particular patient groups may vary, including pregnant women, children, and persons with learning difficulties, it is important that DR management is personalised in such particular patient groups. First choice therapy needs to be individualised in these cases and may be intravitreal steroids rather than the standard choice of anti-VEGF agents. Some of these, but not all, are discussed in this document.
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Senthil S, Dada T, Das T, Kaushik S, Puthuran GV, Philip R, Rani PK, Rao H, Singla S, Vijaya L. Neovascular glaucoma - A review. Indian J Ophthalmol 2021; 69:525-534. [PMID: 33595466 PMCID: PMC7942095 DOI: 10.4103/ijo.ijo_1591_20] [Citation(s) in RCA: 64] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
Neovascular glaucoma (NVG) is a sight-threatening secondary glaucoma characterized by appearance of new vessels over the iris and proliferation of fibrovascular tissue in the anterior chamber angle. Retinal ischemia is the common driving factor and common causes are central retinal vein occlusion, proliferative diabetic retinopathy, and ocular ischemic syndrome. The current rise in the prevalence of NVG is partly related to increase in people with diabetes. A high index of suspicion and a thorough anterior segment evaluation to identify the early new vessels on the iris surface or angle are essential for early diagnosis of NVG. With newer imaging modalities such as the optical coherence tomography angiography and newer treatment options such as the anti-vascular endothelial growth factor, it is possible to detect retinal ischemia early, tailor appropriate treatment, monitor disease progression, and treatment response. The management strategies are aimed at reducing the posterior segment ischemia, reduce the neovascular drive, and control the elevated intraocular pressure. This review summarizes the causes, pathogenesis, and differential diagnoses of NVG, and the management guidelines. We also propose a treatment algorithm of neovascular glaucoma.
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Affiliation(s)
- Sirisha Senthil
- VST Glaucoma Center, L V Prasad Eye Institute, Banjara Hills, Hyderabad, Telangana, India
| | - Tanuj Dada
- Dr. Rajendra Prasad Center for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India
| | - Taraprasad Das
- Srimathi Kanuri Santhamma Centre for Vitreoretinal Diseases, L V Prasad Eye Institute, Hyderabad, Telangana, India
| | - Sushmita Kaushik
- Advanced Eye Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | | | - Reni Philip
- Smt Jadhavabai Nathmal Singhvee Glaucoma Services, Sankara Nethralaya, Chennai, Tamil Nadu, India
| | - Padmaja Kumari Rani
- Srimathi Kanuri Santhamma Centre for Vitreoretinal Diseases, L V Prasad Eye Institute, Hyderabad, Telangana, India
| | - Harsha Rao
- Narayana Nethralaya, Bangalore, Karnataka, India
| | - Shaveta Singla
- VST Glaucoma Center, L V Prasad Eye Institute, Banjara Hills, Hyderabad, Telangana, India
| | - Lingam Vijaya
- Smt Jadhavabai Nathmal Singhvee Glaucoma Services, Sankara Nethralaya, Chennai, Tamil Nadu, India
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Nian S, Lo ACY, Mi Y, Ren K, Yang D. Neurovascular unit in diabetic retinopathy: pathophysiological roles and potential therapeutical targets. EYE AND VISION 2021; 8:15. [PMID: 33931128 PMCID: PMC8088070 DOI: 10.1186/s40662-021-00239-1] [Citation(s) in RCA: 62] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Accepted: 04/02/2021] [Indexed: 02/06/2023]
Abstract
Diabetic retinopathy (DR), one of the common complications of diabetes, is the leading cause of visual loss in working-age individuals in many industrialized countries. It has been traditionally regarded as a purely microvascular disease in the retina. However, an increasing number of studies have shown that DR is a complex neurovascular disorder that affects not only vascular structure but also neural tissue of the retina. Deterioration of neural retina could precede microvascular abnormalities in the DR, leading to microvascular changes. Furthermore, disruption of interactions among neurons, vascular cells, glia and local immune cells, which collectively form the neurovascular unit, is considered to be associated with the progression of DR early on in the disease. Therefore, it makes sense to develop new therapeutic strategies to prevent or reverse retinal neurodegeneration, neuroinflammation and impaired cell-cell interactions of the neurovascular unit in early stage DR. Here, we present current perspectives on the pathophysiology of DR as a neurovascular disease, especially at the early stage. Potential novel treatments for preventing or reversing neurovascular injuries in DR are discussed as well.
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Affiliation(s)
- Shen Nian
- Department of Pathology, Xi'an Medical University, Xi'an, Shaanxi Province, China.
| | - Amy C Y Lo
- Department of Ophthalmology, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong
| | - Yajing Mi
- Institute of Basic Medicine Science, Xi'an Medical University, Xi'an, Shaanxi Province, China
| | - Kai Ren
- Department of Biochemistry and Molecular Biology, Xi'an Medical University, Xi'an, Shaanxi Province, China
| | - Di Yang
- Department of Ophthalmology, First Affiliated Hospital of Kunming Medical University, Kunming Medical University, Kunming, Yunnan Province, China.
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Gao L, Zhao W, Yang JK, Qin MZ. Proliferative diabetic retinopathy in patients with type 2 diabetes correlates with the presence of atherosclerosis cardiovascular disease. Diabetol Metab Syndr 2021; 13:48. [PMID: 33902673 PMCID: PMC8077820 DOI: 10.1186/s13098-021-00666-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Accepted: 04/13/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Atherosclerosis cardiovascular disease (ASCVD) is the main cause of morbidity and mortality in type 2 diabetes mellitus (T2DM). As most diabetic patients with ASCVD are asymptomatic, it is most neglected in clinical practice. For this reason, identifying high-risk ASCVD population with intensified treatment is very important. In recent years, the relationship between diabetic retinopathy (DR) and ASCVD has caused much academic concern, but the results are inconsistent. Moreover, whether all grades of DR increase the risk of ASCVD remains controversial. Most importantly, very few data can be found in China. OBJECTIVE Our aim is to discuss whether all grades of DR increase the risk of ASCVD after adjustment for the traditional cardiovascular risk factors and to assess the independent contribution of DR to cardiovascular events in patients with T2DM, hoping to provide more evidence for early identification of ASCVD. RESEARCH DESIGN AND METHODS A total of 425 T2DM patients with complete physical and biochemical data were included in the study. The grade of DR was assessed with two 45 color digital retinal images. Based on the presence of history of ASCVD, 425 T2DM patients were divided into 2 groups: ASCVD group and non-ASCVD group. RESULTS ASCVD patients were older and had a significantly higher fasting plasma glucose (FPG) and glycated haemoglobin (HbA1c) and proportion of history of ASCVD. At the same time, they were more likely to be females, and had lower level of alcohol and calculated glomerular filtration rate (eGFR) than non-ASCVD patients. Their trend to develop DR with ASCVD was significantly higher than patients with non-ASCVD (χ2 = 5.805, P = 0.016). DR was an independent statistical indicator of the presence of ASCVD [odds ratio (OR) (95% CI): 2.321 (1.152-4.678), P = 0.018]. Furthermore, when DR was divided into non-proliferative retinopathy (NPDR) and proliferative retinopathy (PDR) according to its severity, only PDR was significantly associated with incident ASCVD [OR (95% CI): 8.333 (1.813-38.304), P = 0.006]. After adjusting for traditional ASCVD risk factors, such an association still existed [OR (95% CI): 7.466 (1.355-41.137), P = 0.021]. CONCLUSION DR associates strongly with ASCVD in the Chinese population with T2DM. With the increasing severity of DR, the risk of ASCVD also increases. After adjustment for traditional risk factors, PDR is still an independent risk marker for ASCVD.
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Affiliation(s)
- Lu Gao
- Department of Geriatrics, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China
| | - Wei Zhao
- Department of Geriatrics, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China
| | - Jin-Kui Yang
- Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Ming-Zhao Qin
- Department of Geriatrics, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China.
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