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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

delta Opioid Receptor Agonism Preserves the Retinal Pigmented Epithelial Cell Tight Junctions and Ameliorates the Retinopathy in Experimental Diabetes

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Author(s):
Lopes de Faria, Jacqueline M. [1] ; Duarte, Diego A. [1] ; Simo, Rafael [2, 3] ; Garcia-Ramirez, Marta [2, 3] ; Datilo, Marcella N. [1] ; Pasqualetto, Francieli C. [1] ; Lopes de Faria, Jose B. [1]
Total Authors: 7
Affiliation:
[1] State Univ Campinas UNICAMP, Fac Med Sci, Invest Diabet Complicat, Renal Pathophysiol Lab, Campinas, SP - Brazil
[2] Vall dHebron Res Inst VHIR, Barcelona - Spain
[3] CIBERDEM, Barcelona - Spain
Total Affiliations: 3
Document type: Journal article
Source: INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE; v. 60, n. 12, p. 3842-3853, SEP 2019.
Web of Science Citations: 0
Abstract

PURPOSE. Outer blood retinal barrier breakdown is a neglected feature of diabetic retinopathy (DR). We demonstrated that the agonism of the delta opioid receptor (DOR) by epicatechin preserves the tight junction proteins in ARPE-19 cells under diabetic conditions. Presently, we aimed to evaluate the possible role of the DOR on the maintenance of tight junction of RPE layer and on the early markers of experimental DR. METHODS. DR markers and external retinal tight junction proteins were evaluated in CL57B diabetic mice submitted to intravitreous injection of short hairpin RNA (shRNA)-DOR (10(8) transducing units {[}TU]/mL) treated or not with DOR agonist (0.05 g/animal/d of epicatechin in drinking water) for 16 weeks. The presence of DOR in human retina from postmortem eyes from diabetic and nondiabetic donors were also performed. RESULTS. DOR is present in RPE layer and in neuro retina. The treatment with DOR agonist prevented the upregulation of the early markers of retinopathy (glial fibrillary acidic protein, VEGF) and the downregulation of pigment epithelium-derived factor, occludin, claudin-1, and zonula occludens-1 tight junction expressions. The silencing of DOR in retina of diabetic mice partially abolished the protective effects of epicatechin. In human retina specimens, DOR is present throughout the retina, similarly in nondiabetic and diabetic donors. CONCLUSIONS. This set of experiments strongly indicates that the DOR agonism preserves RPE tight junctions and reduces the early markers of retinopathy in model of diabetes. These novel findings designate DOR as a potential therapeutic tool to treat DR with preservation of the RPE tight junction proteins. (AU)

FAPESP's process: 15/23258-9 - The role of AMPK in the neural-retina and blood-retinal barrier in a model of experimental diabetes in mice knockout for AMPKalpha-1 and AMPKalpha-2. New perspective in the pharmacological treatment of diabetic retinopathy
Grantee:Diego Andreazzi Duarte
Support Opportunities: Scholarships in Brazil - Post-Doctorate