neuroretina is a novel mineralocorticoid target: aldosterone up-regulates ion and water channels in Müller glial cells

• Published in: The FASEB journal 2010-09, Vol.24 (9), p.3405-3415
• Main Authors: Zhao, Min, Valamanesh, Fatemeh, Celerier, Isabelle, Savoldelli, Michèle, Jonet, Laurent, Jeanny, Jean-Claude, Jaisser, Frederic, Farman, Nicolette, Behar-Cohen, Francine
• Format: Article
• Language: English
• Subjects: Aldosterone - pharmacology; Animals; aquaporin 4; Aquaporin 4 - genetics; Aquaporin 4 - metabolism; Blotting, Western; Cell Line; Cells, Cultured; Dexamethasone - pharmacology; ENaC sodium channel; Epithelial Sodium Channels - genetics; Epithelial Sodium Channels - metabolism; Female; Fluorescent Antibody Technique; Gene Expression - drug effects; Gene Expression - genetics; glucocorticoids; Humans; Immunohistochemistry; Kir 4.1 potassium channel; mineralocorticoid receptor; Polymerase Chain Reaction; Potassium Channels, Inwardly Rectifying - genetics; Potassium Channels, Inwardly Rectifying - metabolism; Rats; Rats, Inbred Lew; Receptors, Glucocorticoid - genetics; Receptors, Glucocorticoid - metabolism; Receptors, Mineralocorticoid - genetics; Receptors, Mineralocorticoid - metabolism; Retina - cytology; Retina - metabolism
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fj.09-154344

Glucocorticoids reduce diabetic macular edema, but the mechanisms underlying glucocorticoid effects are imperfectly elucidated. Glucocorticoids may bind to glucocorticoid (GR) and mineralocorticoid (MR) receptors. We hypothesize that MR activation may influence retinal hydration. The effect of the MR agonist aldosterone (24 h) on ion/water channel expression (real-time PCR, Western blot, immunofluorescence) was investigated on cultured retinal Müller glial cells (RMGs, which contribute to fluid homeostasis in the retina), in Lewis rat retinal explants, and in retinas from aldosterone-injected eyes. We evidenced cell-specific expression of MR, GR, and 11-β-hydroxysteroid dehydrogenase type II. Aldosterone significantly enhances expression of sodium and potassium channels ENaC-α (6.5-fold) and Kir4.1 (1.9-fold) through MR and GR occupancy, whereas aquaporin 4 (AQP4, 2.9-fold) up-regulation is MR-selective. Aldosterone intravitreous injection induces retinal swelling (24% increase compared to sham-injected eyes) and activation of RMGs. It promotes additional localization of Kir4.1 and AQP4 toward apical microvilli of RMGs. Our results highlight the mineralocorticoid-sensitivity of the neuroretina and show that aldosterone controls hydration of the healthy retina through regulation of ion/water channels expression in RMGs. These results provide a rationale for future investigations of abnormal MR signaling in the pathological retina.--Zhao, M., Valamanesh, F., Celerier, I., Savoldelli, M., Jonet, L., Jeanny, J.-C., Jaisser, F., Farman, N., Behar-Cohen, F. The neuroretina is a novel mineralocorticoid target: aldosterone up-regulates ion and water channels in Müller glial cells.