RT Journal Article
T1 Mineralocorticoid Receptor Pathway and Its Antagonism in a Model of Diabetic Retinopathy
A1 Zhao, Min
A1 Gelize, Emmanuelle
A1 Levy, Rinath
A1 Moulin, Alexandre
A1 Azan, Frederic
A1 Berdugo, Marianne
A1 Naud, Marie-Cristine
A1 Guegan, Justine
A1 Delaunay, Kimberley
A1 Pussard, Eric
A1 Lassiaz, Patricia
A1 Bravo Osuna, Irene
A1 Herrero Vanrell, María Del Rocío
A1 Behar-Cohen, Francine
AB Diabetic retinopathy remains a major cause of vision loss worldwide. Mineralocorticoid receptor (MR) pathway activation contributes to diabetic nephropathy, but its role in retinopathy is unknown. In this study, we show that MR is overexpressed in the retina of type 2 diabetic Goto-Kakizaki (GK) rats and humans and that cortisol is the MR ligand in human eyes. Lipocalin 2 and galectin 3, two biomarkers of diabetes complications regulated by MR, are increased in GK and human retina. The sustained intraocular delivery of spironolactone, a steroidal mineralocorticoid antagonist, decreased the early and late pathogenic features of retinopathy in GK rats, such as retinal inflammation, vascular leakage, and retinal edema, through the upregulation of genes encoding proteins known to intervene in vascular permeability such as Hey1, Vldlr, Pten, Slc7a1, Tjp1, Dlg1, and Sesn2 but did not decrease VEGF. Spironolactone also normalized the distribution of ion and water channels in macroglial cells. These results indicate that MR is activated in GK and human diabetic retina and that local MR antagonism could be a novel therapeutic option for diabetic retinopathy.
YR 2021
FD 2021-08-12
LK https://hdl.handle.net/20.500.14352/117956
UL https://hdl.handle.net/20.500.14352/117956
LA eng
NO Zhao M, Gelize E, Levy R, Moulin A, Azan F, Berdugo M, et al. Mineralocorticoid receptor pathway and its antagonism in a model of diabetic retinopathy. Diabetes [Internet]. 1 de noviembre de 2021 [citado 10 de febrero de 2025];70(11):2668-82. Disponible en: https://diabetesjournals.org/diabetes/article/70/11/2668/123873/Mineralocorticoid-Receptor-Pathway-and-Its
NO INSERM,  (ANR Mineraloret  and )
NO Agence Nationale de la Recherche
NO Fondation de l’Avenir
NO The Abraham J. & Phyllis Katz Foundation
NO Instituto de Salud Carlos III
DS Docta Complutense
RD 10 abr 2025