Mineralocorticoid Receptor Pathway and Its Antagonism in a Model of Diabetic Retinopathy.

Details

Serval ID
serval:BIB_E076C04E3DE4
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Mineralocorticoid Receptor Pathway and Its Antagonism in a Model of Diabetic Retinopathy.
Journal
Diabetes
Author(s)
Zhao M., Gelize E., Levy R., Moulin A., Azan F., Berdugo M., Naud M.C., Guegan J., Delaunay K., Pussard E., Lassiaz P., Bravo-Osuna I., Herrero-Vanrell R., Behar-Cohen F.
ISSN
1939-327X (Electronic)
ISSN-L
0012-1797
Publication state
Published
Issued date
11/2021
Peer-reviewed
Oui
Volume
70
Number
11
Pages
2668-2682
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
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.
Keywords
Animals, Delayed-Action Preparations, Diabetes Mellitus, Type 2/metabolism, Diabetic Retinopathy/etiology, Female, Gene Expression Regulation/drug effects, Humans, Hydrocortisone/metabolism, Male, Mineralocorticoid Receptor Antagonists/administration & dosage, Mineralocorticoid Receptor Antagonists/chemistry, Mineralocorticoid Receptor Antagonists/pharmacology, Polylactic Acid-Polyglycolic Acid Copolymer/chemistry, Rats, Rats, Inbred Strains, Receptors, Mineralocorticoid/genetics, Receptors, Mineralocorticoid/metabolism, Retina/pathology, Retinal Neurons/drug effects, Retinal Neurons/pathology, Spironolactone/administration & dosage, Spironolactone/chemistry, Spironolactone/pharmacology, Up-Regulation, Vitreous Body
Pubmed
Create date
14/09/2021 12:25
Last modification date
03/03/2022 6:34
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