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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.<\/jats:p>","DOI":"10.2337\/db21-0099","type":"journal-article","created":{"date-parts":[[2021,8,23]],"date-time":"2021-08-23T08:45:55Z","timestamp":1629708355000},"page":"2668-2682","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":30,"title":["Mineralocorticoid Receptor Pathway and Its Antagonism in a Model of Diabetic Retinopathy"],"prefix":"10.2337","volume":"70","author":[{"given":"Min","family":"Zhao","sequence":"first","affiliation":[{"name":"Centre de Recherche des Cordeliers, Sorbonne Universit\u00e9, Universit\u00e9 de Paris, Inserm, From Physiopathology of Retinal Diseases to Clinical Advances, Paris, 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