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

Abstract

Citation: Lopes de Faria JM, Duarte DA, Simó R, et al. d opioid receptor agonism preserves the retinal pigmented epithelial cell tight junctions and ameliorates the retinopathy in experimental diabetes. Invest Ophthalmol Vis Sci. 2019;60:3842-3853. https://doi.org/10.1167/iovs.19-26761PURPOSE. Outer blood retinal barrier breakdown is a neglected feature of diabetic retinopathy (DR). We demonstrated that the agonism of the d 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.

Renal protection induced by physical exercise may be mediated by the irisin/AMPK axis in diabetic nephropathy

“…The samples (renal cortex and gastrocnemius muscle) and Western blots were prepared and performed as previously described 29 , 30 . Protein quantification was determined using the Bradford method 31 .…”

Role of LINC01592 in TGF-β1-induced epithelial-mesenchymal transition of retinal pigment epithelial cells

“…Cell viability was calculated using the following formula: Cell viability (%) = [A (medication) - B (blank)]/[C (0 medication) - B (blank)] × 100, whereby A is the absorption of experimental group wells with cells, CCK-8 solution, and culture medium, following transfection with plasmid and intervention with or without TGF-β1; B is the absorption of wells with CCK-8 solution and culture medium, but without cells; and C is the absorption of control group wells with cells, CCK-8 solution, and culture medium, but without plasmid transfection or TGF-β1 intervention of [ 34 ]. All experiments were repeated three times.…”

The Healthy and Diseased Retina Seen through Neuron–Glia Interactions

“…Early changes in the electrical activity, thickness of the human retina, and electrophysiological and visual perceptual changes prior to vascular changes have also been shown [75,383]; for a review, please read [382]. The RPE also showed oxidative stress [4,384], tight junction destruction [385][386][387], and apoptosis [388]. Therefore, all cell types that constitute the retina are affected by persistent hyperglycemia in diabetes and contributed to its disastrous outcome.…”