Pathogenic Effects of Mineralocorticoid Pathway Activation in Retinal Pigment Epithelium.

Détails

ID Serval
serval:BIB_29FED9B83112
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Pathogenic Effects of Mineralocorticoid Pathway Activation in Retinal Pigment Epithelium.
Périodique
International journal of molecular sciences
Auteur(s)
Canonica J., Zhao M., Favez T., Gelizé E., Jonet L., Kowalczuk L., Guegan J., Le Menuet D., Viengchareun S., Lombès M., Pussard E., Arsenijevic Y., Behar-Cohen F.
ISSN
1422-0067 (Electronic)
ISSN-L
1422-0067
Statut éditorial
Publié
Date de publication
05/09/2021
Peer-reviewed
Oui
Volume
22
Numéro
17
Pages
9618
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Résumé
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-retina 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-an MR-specific agonist, or cortisol or cortisol + RU486-a 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-mesenchymal 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.
Mots-clé
corticoids, eye, mineralocorticoid, retina, retinal pigment epithelium, transcriptional regulation
Pubmed
Web of science
Open Access
Oui
Financement(s)
Autre / FNS 320030_156401
Création de la notice
17/09/2021 17:04
Dernière modification de la notice
25/09/2021 5:37
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