{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T21:59:00Z","timestamp":1790632740604,"version":"4.1.0"},"reference-count":65,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2021,9,5]],"date-time":"2021-09-05T00:00:00Z","timestamp":1630800000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ROCK-SUR-MER 15 CE-18 0032"],"award-info":[{"award-number":["ROCK-SUR-MER 15 CE-18 0032"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"name":"fond national Suisse","award":["# 320030 15640"],"award-info":[{"award-number":["# 320030 15640"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Glucocorticoids are amongst the most used drugs to treat retinal diseases of various origins. Yet, the transcriptional regulations induced by glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) activation in retinal pigment epithelium cells (RPE) that form the outer blood\u2013retina barrier are unknown. Levels of endogenous corticoids, ligands for MR and GR, were measured in human ocular media. Human RPE cells derived from induced pluripotent stem cells (iRPE) were used to analyze the pan-transcriptional regulations induced by aldosterone\u2014an MR-specific agonist, or cortisol or cortisol + RU486\u2014a GR antagonist. The retinal phenotype of transgenic mice that overexpress the human MR (P1.hMR) was analyzed. In the human eye, the main ligand for GR and MR is cortisol. The iRPE cells express functional GR and MR. The subset of genes regulated by aldosterone and by cortisol + RU-486, and not by cortisol alone, mimics an imbalance toward MR activation. They are involved in extracellular matrix remodeling (CNN1, MGP, AMTN), epithelial\u2013mesenchymal transition, RPE cell proliferation and migration (ITGB3, PLAUR and FOSL1) and immune balance (TNFSF18 and PTX3). The P1.hMR mice showed choroidal vasodilation, focal alteration of the RPE\/choroid interface and migration of RPE cells together with RPE barrier function alteration, similar to human retinal diseases within the pachychoroid spectrum. RPE is a corticosteroid-sensitive epithelium. MR pathway activation in the RPE regulates genes involved in barrier function, extracellular matrix, neural regulation and epithelial differentiation, which could contribute to retinal pathology.<\/jats:p>","DOI":"10.3390\/ijms22179618","type":"journal-article","created":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T13:15:56Z","timestamp":1630934156000},"page":"9618","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Pathogenic Effects of Mineralocorticoid Pathway Activation in Retinal Pigment Epithelium"],"prefix":"10.3390","volume":"22","author":[{"given":"J\u00e9r\u00e9mie","family":"Canonica","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, 15 rue de l\u2019Ecole de M\u00e9decine, 75006 Paris, France"},{"name":"Department of Ophthalmology, Jules Gonin Eye Hospital, Fondation Asile des Aveugles, University of Lausanne, 1004 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5418-7275","authenticated-orcid":false,"given":"Min","family":"Zhao","sequence":"additional","affiliation":[{"name":"Centre de Recherche des Cordeliers, Sorbonne Universit\u00e9, Universit\u00e9 de Paris, Inserm, From Physiopathology of Retinal Diseases to Clinical Advances, 15 rue de l\u2019Ecole de M\u00e9decine, 75006 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Favez","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Jules Gonin Eye Hospital, Fondation Asile des Aveugles, University of Lausanne, 1004 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuelle","family":"Geliz\u00e9","sequence":"additional","affiliation":[{"name":"Centre de Recherche des Cordeliers, Sorbonne Universit\u00e9, Universit\u00e9 de Paris, Inserm, From Physiopathology of Retinal Diseases to Clinical Advances, 15 rue de l\u2019Ecole de M\u00e9decine, 75006 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Jonet","sequence":"additional","affiliation":[{"name":"Centre de Recherche des Cordeliers, Sorbonne Universit\u00e9, Universit\u00e9 de Paris, Inserm, From Physiopathology of Retinal Diseases to Clinical Advances, 15 rue de l\u2019Ecole de M\u00e9decine, 75006 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Kowalczuk","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Jules Gonin Eye Hospital, Fondation Asile des Aveugles, University of Lausanne, 1004 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justine","family":"Guegan","sequence":"additional","affiliation":[{"name":"Institut du Cerveau, ICM, iCONICS, H\u00f4pital de la Piti\u00e9-Salp\u00eatri\u00e8re, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damien","family":"Le Menuet","sequence":"additional","affiliation":[{"name":"Physiologie et Physiopathologie Endocriniennes, Universit\u00e9 Paris-Saclay, Inserm, 94276 Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4280-3250","authenticated-orcid":false,"given":"Say","family":"Viengchareun","sequence":"additional","affiliation":[{"name":"Physiologie et Physiopathologie Endocriniennes, Universit\u00e9 Paris-Saclay, Inserm, 94276 Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Lomb\u00e8s","sequence":"additional","affiliation":[{"name":"Physiologie et Physiopathologie Endocriniennes, Universit\u00e9 Paris-Saclay, Inserm, 94276 Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Pussard","sequence":"additional","affiliation":[{"name":"Physiologie et Physiopathologie Endocriniennes, Universit\u00e9 Paris-Saclay, Inserm, 94276 Le Kremlin-Bic\u00eatre, France"},{"name":"Assistance Publique\u2014H\u00f4pitaux de Paris, H\u00f4pital Bic\u00eatre, Service de G\u00e9n\u00e9tique Mol\u00e9culaire et d\u2019Hormonologie, 94276 Le Kremlin Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvan","family":"Arsenijevic","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Jules Gonin Eye Hospital, Fondation Asile des Aveugles, University of Lausanne, 1004 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8571-9513","authenticated-orcid":false,"given":"Francine","family":"Behar-Cohen","sequence":"additional","affiliation":[{"name":"Centre de Recherche des Cordeliers, Sorbonne Universit\u00e9, Universit\u00e9 de Paris, Inserm, From Physiopathology of Retinal Diseases to Clinical Advances, 15 rue de l\u2019Ecole de M\u00e9decine, 75006 Paris, France"},{"name":"Assistance Publique\u2014H\u00f4pitaux de Paris, H\u00f4pital Cochin Ophthalmopole, 75014 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1136\/bjophthalmol-2017-311258","article-title":"Prevalence and causes of vision loss in high-income countries and in Eastern and Central Europe in 2015: Magnitude, temporal trends and projections","volume":"102","author":"Bourne","year":"2018","journal-title":"Br. 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