δ Opioid receptor agonism preserves the retinal pigmented epithelial cell tight junctions and ameliorates the retinopathy in experimental diabetes
De Faria, J. M. L. (Renal Pathophysiology Laboratory Investigation on Diabetes Complications. Faculty of Medical Sciences. State University of Campinas (UNICAMP))
Duarte, D. A. (Renal Pathophysiology Laboratory Investigation on Diabetes Complications. Faculty of Medical Sciences. State University of Campinas (UNICAMP))
Simó, R. (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Garcia-Ramírez, Marta (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Dátilo, M. N. (Renal Pathophysiology Laboratory Investigation on Diabetes Complications. Faculty of Medical Sciences. State University of Campinas (UNICAMP))
Pasqualetto, F. C. (Renal Pathophysiology Laboratory Investigation on Diabetes Complications. Faculty of Medical Sciences. State University of Campinas (UNICAMP))
De Faria, J. B. L. (Renal Pathophysiology Laboratory Investigation on Diabetes Complications. Faculty of Medical Sciences. State University of Campinas (UNICAMP))
Universitat Autònoma de Barcelona

Fecha:	2019
Resumen:	PURPOSE. Outer blood retinal barrier breakdown is a neglected feature of diabetic retinopathy (DR). We demonstrated that the agonism of the δ 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 (108 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.
Nota:	Supported by the European Foundation for Study of Diabetes and Sanofi in the Collaborative Clinical Diabetes Research between European and Non-European Countries Programme. DAD received a scholarship from FAPESP (2015/23258-9).
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució i la comunicació pública de l'obra, sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Diabetic retinopathy ; Diabetes ; D opioid receptor ; Retinal pigmented epithelial
Publicado en:	Investigative Ophthalmology & Visual Science, Vol. 60 Núm. 12 (january 2019) , p. 3842-3853, ISSN 1552-5783

DOI: 10.1167/iovs.19-26761

12 p, 2.4 MB

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