The Role Of Mineralocorticoid Regulation On Hydo-ionic Retinal Homeostasis: Implication For Macular Edema Treatment

Abstract

Purpose: : Gluccorticoids (GC) are used to treat macular edema but the mechanisms underlying this effect remain poorly understood. Since GC acts through gluco (GR) and mineralocorrticoid receptor (MR) activation, we have evaluated whether MR was involved in the neuroretina homeostais and more specifically its hydro ionic control.

Methods: : We have eva;uated the shot term effect of the MR agonist aldosterone on ion/water channels expression (real-time PCR, western blot, immunofluorescence) on cultured retinal Müller glial cells, in Lewis rat retinal explants and in retinas from aldosterone-injected eyes.

Results: : We evidenced cell-specific expression of MR, GR and 11-beta hydroxysteroid dehydrogenase type II in the neuroretina demonstrating that the retina is a mineralo sensitive tissue. 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, while 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 RMG. It promotes additional localization of Kir4.1 and AQP4 towards apical microvilli of RMG.

Conclusions: : Our results show that aldosterone controls hydration of the healthy retina through regulation of ion/water channels expression in RMG. These results provide a rationale for future investigations of abnormal MR signalling in the pathologic retina.

Keywords: corticosteroids • Muller cells • edema