Related Experiment Video
Updated: Jun 24, 2026
Efficient Dissection and Culture of Primary Mouse Retinal Pigment Epithelial Cells
Published on: February 10, 2021
Pathogenic Effects of Mineralocorticoid Pathway Activation in Retinal Pigment Epithelium
Jérémie Canonica1,2, Min Zhao1, Tatiana Favez2
1Centre de Recherche des Cordeliers, Sorbonne Université, Université de Paris, Inserm, From Physiopathology of Retinal Diseases to Clinical Advances, 15 rue de l'Ecole de Médecine, 75006 Paris, France.
Abstract:
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.
Insights
Mineralocorticoid receptor (MR) activation in retinal pigment epithelium (RPE) cells influences genes involved in extracellular matrix remodeling and cell migration, potentially contributing to retinal diseases like pachychoroid spectrum disorders.
Area of Science:
- Ophthalmology
- Molecular Biology
- Cell Biology
Background:
- Glucocorticoids are widely used for retinal diseases, but the specific roles of glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) in retinal pigment epithelium (RPE) cells remain unclear.
- Understanding these roles is crucial as RPE cells form the outer blood-retina barrier, essential for retinal health.
Purpose of the Study:
- To investigate the transcriptional regulations induced by GR and MR activation in human RPE cells.
- To analyze the retinal phenotype of mice with MR overexpression and its relation to human retinal diseases.
Main Methods:
- Measured endogenous corticoids in human ocular media.
- Utilized human induced pluripotent stem cell-derived RPE (iRPE) cells to study transcriptional changes induced by MR-specific and GR-specific agonists/antagonists.
- Analyzed the retinal phenotype of transgenic mice overexpressing the human MR (P1.hMR).
Main Results:
- Cortisol is the primary ligand for both GR and MR in the human eye.
- MR pathway activation in RPE cells, distinct from GR activation, regulates genes involved in extracellular matrix remodeling, epithelial-mesenchymal transition, cell proliferation, migration, and immune balance.
- P1.hMR mice exhibited RPE barrier dysfunction, choroidal vasodilation, and RPE cell migration, mirroring aspects of human pachychoroid spectrum diseases.
Conclusions:
- Retinal pigment epithelium is sensitive to corticosteroids.
- MR pathway activation in RPE cells plays a significant role in regulating genes critical for barrier function, extracellular matrix, neural regulation, and epithelial differentiation.
- These MR-driven changes in RPE may contribute to the pathogenesis of various retinal diseases.
