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Dabas A, Goyal B. Delineating the tryptophan-galactosylamine conjugate mediated structural distortions in Aβ 42 protofibrils. Phys Chem Chem Phys 2025; 27:7336-7355. [PMID: 40123533 DOI: 10.1039/d4cp03330b] [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: 03/25/2025]
Abstract
Amyloid-β (Aβ) fibrillation into neurotoxic soluble oligomers and mature fibrils is mainly responsible for the etiology of Alzheimer's disease (AD). A recent study revealed 61% disaggregation of the pre-formed Aβ42 fibrils upon incubating with a highly soluble tryptophan-galactosylamine conjugate, WGalNAc. WGalNAc displayed no toxicity and increased the viability of SH-SY5Y cells up to 62.9 ± 2% with an EC50 value of 2.3 μM against Aβ42 pre-formed fibrils. However, the key interactions and disruptive mechanism of WGalNAc against Aβ fibrils remain elusive. Thus, mechanistic insights into the disruptive potential of WGalNAc against Aβ42 protofibrils (PDB: 5OQV) were examined using molecular dynamics (MD) simulations. The molecular docking depicted a favourable binding energy (-6.60 kcal mol-1) and interaction of WGalNAc with the central hydrophobic core (CHC) region of chain A of the 5OQV protofibril. The MD simulations depicted that WGalNAc disrupted the contacts among Ala2, Phe4, Leu34, and Val36 in the hydrophobic core 1 of the 5OQV protofibril responsible for maintaining the stability of the LS-shaped 5OQV protofibril. WGalNAc binds favourably to the 5OQV protofibril (ΔGbinding = -21.76 ± 2.40 kcal mol-1) with a significant contribution from the van der Waals interaction term. Notably, the binding affinity between the neighbouring chains of the 5OQV protofibril was significantly reduced from -134.31 ± 11.12 to -121.88 ± 1.95 kcal mol-1 upon the incorporation of WGalNAc, which is consistent with the ThT kinetic results that revealed disaggregation of the pre-formed Aβ42 fibrils upon incubating with WGalNAc. The in silico ADMET properties of WGalNAc showed its ability as a promising therapeutic candidate due to its blood-brain barrier (BBB) permeability, extended half-life, and non-toxic profile. The MD simulations illuminated the binding interactions of WGalNAc with the 5OQV protofibril and provided mechanistic insights into the WGalNAc-mediated structural distortions in the 5OQV protofibril.
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Affiliation(s)
- Arushi Dabas
- Department of Chemistry & Biochemistry, Thapar Institute of Engineering & Technology, Patiala, 147004, Punjab, India.
| | - Bhupesh Goyal
- Department of Chemistry & Biochemistry, Thapar Institute of Engineering & Technology, Patiala, 147004, Punjab, India.
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Ammari W, Chaabene H, Messaoud R. [Anatomical and functional outcomes of the "3+PRN" therapeutic protocol in the treatment of diabetic macular edema]. J Fr Ophtalmol 2024; 47:104234. [PMID: 38875945 DOI: 10.1016/j.jfo.2024.104234] [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: 09/17/2023] [Revised: 02/04/2024] [Accepted: 03/12/2024] [Indexed: 06/16/2024]
Abstract
PURPOSE To evaluate the anatomical and functional results of the "3+PRN" protocol in the treatment of diabetic macular edema (DME), determine the predictive factors for good final visual acuity, and compare it to other protocols. MATERIALS AND METHODS We conducted a retrospective, descriptive, comparative, cross-sectional study of patients with DME, which we dubbed HTSM. All patients were treated with three monthly initial intravitreal injections (IVT) of 1.25mg bevacizumab and followed according to the pro re nata (PRN) protocol for a period of 3years. The protocol was based on a monthly monitoring schedule for the first 3months, then increasingly spaced out over time. "On-demand" treatment was indicated with resumption of bevacizumab IVT in the event of worsening of DME. RESULTS A total of 52 patients were included. The mean age was 65years. Type 2 was the most frequently observed type of diabetes. The mean duration of the PRN protocol was 6months, and the mean number of injections was 6. The mean visual acuity (VA), initially 1/10, improved to 3/10 by the conclusion of the 3+PRN protocol, with an improvement of more than 5 letters in 77.6% of cases. The mean initial central macular thickness (CMT) was 451.5μm. The final mean EMC decreased to 298.5μm, which corresponds to a reduction of 153μm compared to the initial value. The mean subfoveal choroidal thickness, initially 304.2μm, decreased to a mean of 284.5μm at completion. Comparative analysis of the results before and after the PRN protocol confirmed the existence of a statistically significant correlation between VA and CMT (P<0.05). No correlation was observed between age and visual acuity or between initial and final VA. The analysis of the various tomographic parameters and VA revealed a significantly better visual improvement in the group in whom the external limiting membrane (MLE) and ellipsoid zone (ZE) were intact (P=0.04), as well as in the group in whom serous retinal detachment (SRD) was absent (P<0.001). Posterior vitreous detachment (PVD) was the most frequently observed vitreomacular anomaly. The final VA was similar in the groups with and without PVD (P=0.04). CONCLUSION The 3+PRN protocol is effective both functionally and tomographically in the treatment of DME. Various tomographic parameters might influence therapeutic efficacy. However, further in-depth studies are needed to better investigate these parameters.
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Affiliation(s)
- W Ammari
- Service d'ophtalmologie, hôpital universitaire Taher Sfar Mahdia, Jbel Dar Waja 5100, Tunisie; Faculté de médecine de Monastir, Monastir, Tunisie.
| | - H Chaabene
- Service d'ophtalmologie, hôpital universitaire Taher Sfar Mahdia, Jbel Dar Waja 5100, Tunisie; Faculté de médecine de Monastir, Monastir, Tunisie
| | - R Messaoud
- Service d'ophtalmologie, hôpital universitaire Taher Sfar Mahdia, Jbel Dar Waja 5100, Tunisie; Faculté de médecine de Monastir, Monastir, Tunisie
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Sharma S, Daigavane S, Shinde P. Innovations in Diabetic Macular Edema Management: A Comprehensive Review of Automated Quantification and Anti-vascular Endothelial Growth Factor Intervention. Cureus 2024; 16:e54752. [PMID: 38523956 PMCID: PMC10961153 DOI: 10.7759/cureus.54752] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Accepted: 02/23/2024] [Indexed: 03/26/2024] Open
Abstract
Diabetic macular edema (DME) poses a significant threat to the vision and quality of life of individuals with diabetes. This comprehensive review explores recent advancements in DME management, focusing on integrating automated quantification techniques and anti-vascular endothelial growth factor (anti-VEGF) interventions. The review begins with an overview of DME, emphasizing its prevalence, impact on diabetic patients, and current challenges in management. It then delves into the potential of automated quantification, leveraging machine learning and artificial intelligence to improve early detection and monitoring. Concurrently, the role of anti-VEGF therapies in addressing the underlying vascular abnormalities in DME is scrutinized. The review synthesizes vital findings, highlighting the implications for the future of DME management. Promising outcomes from recent clinical trials and case studies are discussed, providing insights into the evolving landscape of personalized medicine approaches. The conclusion underscores the transformative potential of these innovations, calling for continued research, collaboration, and integration of these advancements into clinical practice. This review aims to serve as a roadmap for researchers, clinicians, and industry stakeholders, fostering a collective effort to enhance the precision and efficacy of DME management.
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Affiliation(s)
- Soumya Sharma
- Ophthalmology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Sachin Daigavane
- Ophthalmology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Pranaykumar Shinde
- Ophthalmology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
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Sodhi GS, Haq Z, Aggarwal N, Boucher N, Emerson GG, Hahn P. Evolving Treatment Patterns in Diabetic Macular Edema Between 2015 and 2020. JOURNAL OF VITREORETINAL DISEASES 2023; 7:199-202. [PMID: 37188218 PMCID: PMC10170625 DOI: 10.1177/24741264231156096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/17/2023]
Abstract
Purpose: To explore the recent evolution of diabetic macular edema (DME) treatment practice patterns over 5 years among retina specialists in the United States. Methods: This retrospective analysis assessed 306 700 eyes with newly diagnosed DME from the Vestrum Health database between January 2015 and October 2020. The year-over-year and cumulative 5-year distributions of eyes treated with antivascular endothelial growth factor (anti-VEGF) agents, steroids, focal laser, or any combination and those of untreated eyes were calculated. Changes from baseline visual acuity were assessed. Results: Yearly treatment patterns changed significantly from 2015 (n = 18056) to 2020 (n = 11042). The proportion of untreated patients declined over time (32.7% vs 27.7%; P < .001), the use of anti-VEGF monotherapy increased (43.5% vs 61.8%; P < .001), the use of focal laser monotherapy declined (9.7% vs 3.0%; P < .001), and the use of steroid monotherapy remained stable (0.9% vs 0.7%; P = 1.000). Of eyes that maintained follow-up for 5 years (from 2015 to 2020), 16.3% were untreated while 77.5% were treated with anti-VEGF agents (as monotherapy or combination therapy). Vision gains in treated patients remained approximately stable from 2015 (3.6 letters) to 2020 (3.5 letters). Conclusions: From 2015 to 2020, treatment patterns for DME evolved toward greater anti-VEGF monotherapy, stable steroid monotherapy, less laser monotherapy, and fewer untreated eyes.
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Affiliation(s)
| | - Zeeshan Haq
- Retina Consultants of Minnesota, Edina, MN, USA
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Munayco-Guillén F, Vazquez-Membrillo MA, Garcia-Roa MR, De La Cruz-Vargas JA, García-Perdomo HA, Pichardo-Rodriguez R. Effectiveness of the Use of Three-Dose Intravitreal Ziv-Aflibercept in the Management of Diabetic Macular Edema in a Real-Life Setting. Clin Ophthalmol 2023; 17:1129-1135. [PMID: 37077223 PMCID: PMC10106786 DOI: 10.2147/opth.s398359] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Accepted: 03/03/2023] [Indexed: 04/21/2023] Open
Abstract
Purpose It has been reported that intravitreal Ziv-aflibercept is a safe and effective drug for the treatment of diabetes macular edema (DME). The objective of this study was to evaluate in a real-life setting, the efficacy of intravitreal Ziv-aflibercept in the treatment of DME after the administration of three consecutive monthly doses. Methods A single arm, prospective cohort study. We included patients with DME who received three doses of intravitreal Ziv-aflibercept. Data such as best corrected visual acuity (BCVA) and tomographic biomarkers before treatment and a month after the third dose were collected. DME was staged using the Panozzo classification. Results Thirty-eight patients participated for a total of 53 eyes. The mean age was 59 ± 8.1 years. We observed significant changes after the third dose in the parameters studied (BCVA in LogMAR pre-treatment (0.6 ± 0.33) and post-treatment (0.4 ± 0.29) [p<0.001], macular thickness pre-treatment (501 ± 167 µm) and post-treatment (324 ± 114 µm) [p<0.001], macular volume pre-treatment 10.8 (7.5-17.8) mm3 and post-treatment 9.3 (0-13.6) mm3 [p<0.005]). And 73.6% of the patients presented an advanced severe stage during their pre-treatment evaluation and after post-treatment, 64.2% of the patients no longer presented edema. No systemic or ocular adverse events occurred. Conclusion The use of three consecutive monthly doses of intravitreal Ziv-aflibercept in a real-life setting is effective and safe in the management of diabetic macular edema.
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Affiliation(s)
- Fernando Munayco-Guillén
- Department of Retina and Vitreous Surgery, Instituto Mexicano de Oftalmología (IMO), Querétaro, México
- Universidad Nacional Autónoma de México (UNAM), México City, México
- Correspondence: Fernando Munayco-Guillén, Fray Servando Teresa de Mier 202, Quintas del Marqués, Querétaro, México, Tel +51 985-558886, Email
| | - Miguel Angel Vazquez-Membrillo
- Department of Retina and Vitreous Surgery, Instituto Mexicano de Oftalmología (IMO), Querétaro, México
- Universidad Nacional Autónoma de México (UNAM), México City, México
| | - Marlon Rafael Garcia-Roa
- Department of Retina and Vitreous Surgery, Instituto Mexicano de Oftalmología (IMO), Querétaro, México
- Universidad Nacional Autónoma de México (UNAM), México City, México
| | | | - Herney Andrés García-Perdomo
- Division of Urology/Urooncology, Deparment of Surgery, School of Medicine, Universidad del Valle, Cali, Colombia
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Karti O, Saatci AO. Place of intravitreal dexamethasone implant in the treatment armamentarium of diabetic macular edema. World J Diabetes 2021; 12:1220-1232. [PMID: 34512888 PMCID: PMC8394236 DOI: 10.4239/wjd.v12.i8.1220] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2020] [Revised: 04/25/2021] [Accepted: 07/07/2021] [Indexed: 02/06/2023] Open
Abstract
Diabetic macular edema (DME) is a very important and well-known cause of visual loss in diabetics. Blood–retina barrier disruption and consequent intraretinal fluid accumulation may lead to retinal thickening at the posterior pole namely DME. Even though it is not clearly understood, current evidence suggests that chronic low-grade inflammation characterized with various cytokines has a major role in the occurrence of DME. Clinical trials are continuously shaping our treatment approaches for the eyes with DME. Today, vascular endothelial growth factor (VEGF) inhibitor and steroid administrations are the main alternatives in DME treatment. Dexamethasone (DEX) implant (Ozurdex®; Allergan, Inc., Irvine, CA, United States) was approved by the United States Food & Drug Administration in 2014 for DME treatment. The implant is made up of a biodegradable solid copolymer that is broken down by releasing its active ingredient into the vitreous cavity over time. Biphasic release feature of this sustained-release drug delivery system ensures its efficacy for up to 6 mo with an acceptable and manageable safety profile. DEX implant provides a favorable anatomical and functional outcome in DME as shown in several randomized-controlled studies but has a relatively higher ocular side-effect profile such as increased risk of cataract formation and raised intraocular pressure when compared to the gold standard anti-VEGF agents. Thus, DEX implant becomes the second-line treatment option demonstrating inadequate clinical response to anti-VEGF therapy. However, it can be preferred as the first-line treatment in vitrectomized and pseudophakic eyes. Even in some selected conditions DEX implant is favored over anti-VEGF agents where the use of VEGF-inhibitors is either inappropriate or contraindicated such as the patients with a recent history of a major cardiovascular or cerebrovascular event, pregnancy and noncompliant to frequent visits. This mini-review briefly overviews the efficacy, safety profile and complications of DEX implant and summarizes the outcome of DEX implant administration in major clinical studies on DME treatment.
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Affiliation(s)
- Omer Karti
- Department of Ophthalmology, İzmir Democracy University, İzmir 35330, Turkey
| | - Ali Osman Saatci
- Department of Ophthalmology, Dokuz Eylul University, İzmir 35330, Turkey
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Paul A, Frenkel-Pinter M, Escobar Alvarez D, Milordini G, Gazit E, Zacco E, Segal D. Tryptophan-galactosylamine conjugates inhibit and disaggregate amyloid fibrils of Aβ42 and hIAPP peptides while reducing their toxicity. Commun Biol 2020; 3:484. [PMID: 32879439 PMCID: PMC7468108 DOI: 10.1038/s42003-020-01216-5] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2020] [Accepted: 07/31/2020] [Indexed: 12/14/2022] Open
Abstract
Self-assembly of proteins into amyloid fibrils is a hallmark of various diseases, including Alzheimer's disease (AD) and Type-2 diabetes Mellitus (T2DM). Aggregation of specific peptides, like Aβ42 in AD and hIAPP in T2DM, causes cellular dysfunction resulting in the respective pathology. While these amyloidogenic proteins lack sequence homology, they all contain aromatic amino acids in their hydrophobic core that play a major role in their self-assembly. Targeting these aromatic residues by small molecules may be an attractive approach for inhibiting amyloid aggregation. Here, various biochemical and biophysical techniques revealed that a panel of tryptophan-galactosylamine conjugates significantly inhibit fibril formation of Aβ42 and hIAPP, and disassemble their pre-formed fibrils in a dose-dependent manner. They are also not toxic to mammalian cells and can reduce the cytotoxicity induced by Aβ42 and hIAPP aggregates. These tryptophan-galactosylamine conjugates can therefore serve as a scaffold for the development of therapeutics towards AD and T2DM.
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Affiliation(s)
- Ashim Paul
- Department of Molecular Microbiology and Biotechnology, School of Molecular Cell Biology and Biotechnology, Tel Aviv University, Ramat Aviv, Tel Aviv, 6997801, Israel
| | - Moran Frenkel-Pinter
- Department of Molecular Microbiology and Biotechnology, School of Molecular Cell Biology and Biotechnology, Tel Aviv University, Ramat Aviv, Tel Aviv, 6997801, Israel
| | - Daniela Escobar Alvarez
- Department of Molecular Microbiology and Biotechnology, School of Molecular Cell Biology and Biotechnology, Tel Aviv University, Ramat Aviv, Tel Aviv, 6997801, Israel
| | - Giulia Milordini
- The Maurice Wohl Clinical Neuroscience Institute, King's College London, Brixton, London, SE5 9RT, UK
| | - Ehud Gazit
- Department of Molecular Microbiology and Biotechnology, School of Molecular Cell Biology and Biotechnology, Tel Aviv University, Ramat Aviv, Tel Aviv, 6997801, Israel
| | - Elsa Zacco
- The Maurice Wohl Clinical Neuroscience Institute, King's College London, Brixton, London, SE5 9RT, UK.
- RNA Central Lab, Center for Human Technologies, Istituto Italiano di Tecnologia, 16152, Genova, Italy.
| | - Daniel Segal
- Department of Molecular Microbiology and Biotechnology, School of Molecular Cell Biology and Biotechnology, Tel Aviv University, Ramat Aviv, Tel Aviv, 6997801, Israel.
- Sagol Interdisciplinary School of Neuroscience, Tel Aviv University, Ramat Aviv, Tel Aviv, 6997801, Israel.
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Lai K, Huang C, Li L, Gong Y, Xu F, Zhong X, Lu L, Jin C. Anatomical and functional responses in eyes with diabetic macular edema treated with "1 + PRN" ranibizumab: one-year outcomes in population of mainland China. BMC Ophthalmol 2020; 20:229. [PMID: 32539744 PMCID: PMC7296700 DOI: 10.1186/s12886-020-01510-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2019] [Accepted: 06/09/2020] [Indexed: 10/27/2022] Open
Abstract
BACKGROUND To evaluate the anatomical and functional responses in eyes with diabetic macular edema (DME) treated with ranibizumab under "1 + pro re nata (PRN)" regimen. METHODS This prospective interventional case series included 69 eyes of 69 patients with DME treated with intravitreal injections of 0.5 mg ranibizumab followed by repeated injections as needed. Best-corrected visual acuity (BCVA), central foveal thickness (CFT), subfoveal choroidal thickness (SFCT), and predictive factors for final visual outcomes were assessed. RESULTS Logarithm of minimal angle of resolution (logMAR) BCVA improved from 0.64 ± 0.23 at baseline to 0.56 ± 0.27, 0.53 ± 0.26, 0.47 ± 0.25, 0.44 ± 0.32, 0.47 ± 0.26 and 0.46 ± 0.26 at time-point of months 1, 2, 3, 6, 9, and 12, respectively (P < 0.05 for any follow-up time-point except month 1). CFT decreased from 478.23 ± 172.31 μm at baseline to 349.74 ± 82.21 μm, 313.52 ± 69.62 μm, 292.59 ± 61.07 μm, 284.67 ± 69.85 μm, 268.33 ± 43.03 μm, and 270.39 ± 49.27 μm at above time-points, respectively (P < 0.05). The number of injections was 6.83 times over 12 months' follow-up under "1 + PRN" regimen. Multivariate analysis showed that the factors including age, BCVA at baseline, disruption of ellipsoid zone, posterior vitreous detachment (PVD), and vitreomacular traction (VMT) were correlated with the final BCVA. CONCLUSIONS Intravitreal injections of ranibizumab under "1 + PRN" regimen is a not only effective but also safe way to improve visual acuity of DME patients. And older age, lower baseline BCVA, VMT, and disruption of ellipsoid zone are predictors for final poor BCVA while PVD is a positive predictive factor for good final BCVA. TRIAL REGISTRATION The trial was registered retrospectively in ClinicalTrials.gov on 2 June 2019 (NCT03973138).
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Affiliation(s)
- Kunbei Lai
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 54 South Xianlie Road, Guangzhou, 510060, China
| | - Chuangxin Huang
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 54 South Xianlie Road, Guangzhou, 510060, China
| | - Longhui Li
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 54 South Xianlie Road, Guangzhou, 510060, China
| | - Yajun Gong
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 54 South Xianlie Road, Guangzhou, 510060, China
| | - Fabao Xu
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 54 South Xianlie Road, Guangzhou, 510060, China
| | - Xiaojing Zhong
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 54 South Xianlie Road, Guangzhou, 510060, China
| | - Lin Lu
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 54 South Xianlie Road, Guangzhou, 510060, China
| | - Chenjin Jin
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 54 South Xianlie Road, Guangzhou, 510060, China.
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Affiliation(s)
- Rasha Barham
- Beetham Eye Institute, Joslin Diabetes Center, Boston, MA, USA
| | - Hala El Rami
- Beetham Eye Institute, Joslin Diabetes Center, Boston, MA, USA
| | - Jennifer K. Sun
- Beetham Eye Institute, Joslin Diabetes Center, Boston, MA, USA
- Department of Ophthalmology, Harvard Medical School, Boston, MA, USA
| | - Paolo S. Silva
- Beetham Eye Institute, Joslin Diabetes Center, Boston, MA, USA
- Department of Ophthalmology, Harvard Medical School, Boston, MA, USA
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Shan L, Zheng M, Zhang Y, Qu Y, Niu T, Gu Q, Liu K, Xia X. Correlation of Vascular Endothelial Growth Factor Production with Photochemical Reaction-induced Retinal Edema. Chin Med J (Engl) 2016; 129:2944-2950. [PMID: 27958226 PMCID: PMC5198529 DOI: 10.4103/0366-6999.195463] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
BACKGROUND Retinal edema is the major complication of retinal vein occlusion and diabetic retinopathy; it can damage visual function by influencing macular region. This study was to establish a rat retinal edema model and explore the related VEGF expression and observe the responses to anti-VEGF drugs in this model. METHODS A rat retinal edema model was established by inducing photochemical reaction using a 532 nm laser after the intravenous injection of Erythrosin B. Immediately after the laser treatment, models were given intravitreal injections of Ranibizumab or Conbercept to inhibit VEGF expression, and the changes of retinal thickness were measured. Retinal edema was observed using fundus photography (FP), optical coherence tomography (OCT), and fluoresce in fundus angiography (FFA) at 0, 1, 2, 4, 7 and 14 days after intervention. The retinal VEGF expression was measured using enzyme-linked immunosorbent assay (ELISA) and western blotting at each time point. The rat retinal edema model was also used to verify the function of anti-VEGF polypeptide ZY1. RESULTS Both retinal edema and vascular leakage were clearly observed at 1, 2 and 4 days after photochemical induction and the retinal thickness increased notably over the same period. The retinal VEGF expression peaked at day 1 and retina became thickening simultaneously. After the interventions, the VEGF expression of the Ranibizumab and Conbercept groups decreased at each time point compared to the edema group (26.90 ± 3.57 vs. 40.29 ± 6.68, F = 31.269 on day 1 and 22.36 ± 1.12 vs. 29.92 ± 0.93 F = 163.789 on day 2, both P < 0.01); the mean RT (278 ± 4 vs. 288 ± 3, F = 134.190 on day 1 and 274 ± 7 vs. 284 ± 6, F = 64.367 on day 2, both P < 0.05) and vascular leakage in these groups also decreased. The same results were observed in the ZY1 group, particularly at day 2 (P < 0.05). CONCLUSIONS This retinal edema model induced by a photochemical reaction is reliable and repeatable. Induced edema increases expression of VEGF. This model can be used to test new drugs.
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Affiliation(s)
- Liang Shan
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080; Shanghai Key Laboratory of Fundus Disease, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
| | - Mi Zheng
- Department of Ophthalmology, Fujian Provincial Hospital, Fuzhou, Fujian 350004, China
| | - Yuan Zhang
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080; Shanghai Key Laboratory of Fundus Disease, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
| | - Yuan Qu
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
| | - Tian Niu
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080; Shanghai Key Laboratory of Fundus Disease, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
| | - Qing Gu
- Shanghai Key Laboratory of Fundus Disease, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
| | - Kun Liu
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080; Shanghai Key Laboratory of Fundus Disease, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
| | - Xin Xia
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080; Shanghai Key Laboratory of Fundus Disease, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
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11
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Kozak I. Update on Clinical Trials in Retinal Diseases. Middle East Afr J Ophthalmol 2016; 23:1-2. [PMID: 26957833 PMCID: PMC4759885 DOI: 10.4103/0974-9233.173136] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Affiliation(s)
- Igor Kozak
- Vitreoretinal Division, King Khaled Eye Specialist Hospital, Riyadh, Kingdom of Saudi Arabia
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