Mineralocorticoid receptor is involved in rat and human ocular chorioretinopathy
Min Zhao, … , Frédéric Jaisser, Francine Behar-Cohen
Min Zhao, … , Frédéric Jaisser, Francine Behar-Cohen
Published June 11, 2012
Citation Information: J Clin Invest. 2012;122(7):2672-2679. https://doi.org/10.1172/JCI61427.
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Research Article Ophthalmology

Mineralocorticoid receptor is involved in rat and human ocular chorioretinopathy

Abstract

Central serous chorioretinopathy (CSCR) is a vision-threatening eye disease with no validated treatment and unknown pathogeny. In CSCR, dilation and leakage of choroid vessels underneath the retina cause subretinal fluid accumulation and retinal detachment. Because glucocorticoids induce and aggravate CSCR and are known to bind to the mineralocorticoid receptor (MR), CSCR may be related to inappropriate MR activation. Our aim was to assess the effect of MR activation on rat choroidal vasculature and translate the results to CSCR patients. Intravitreous injection of the glucocorticoid corticosterone in rat eyes induced choroidal enlargement. Aldosterone, a specific MR activator, elicited the same effect, producing choroid vessel dilation -and leakage. We identified an underlying mechanism of this effect: aldosterone upregulated the endothelial vasodilatory K channel KCa2.3. Its blockade prevented aldosterone-induced thickening. To translate these findings, we treated 2 patients with chronic nonresolved CSCR with oral eplerenone, a specific MR antagonist, for 5 weeks, and observed impressive and rapid resolution of retinal detachment and choroidal vasodilation as well as improved visual acuity. The benefit was maintained 5 months after eplerenone withdrawal. Our results identify MR signaling as a pathway controlling choroidal vascular bed relaxation and provide a pathogenic link with human CSCR, which suggests that blockade of MR could be used therapeutically to reverse choroid vasculopathy.

Authors

Min Zhao, Isabelle Célérier, Elodie Bousquet, Jean-Claude Jeanny, Laurent Jonet, Michèle Savoldelli, Olivier Offret, Antoine Curan, Nicolette Farman, Frédéric Jaisser, Francine Behar-Cohen

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Figure 5

OCT and angiographic findings of CSCR Patient 1 before and after eplerenone treatment.

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OCT and angiographic findings of CSCR Patient 1 before and after epleren...
(A) OCT oblique scans of the right eye. At presentation, the patient exhibited a bubble of serous retinal detachment in the macular area, whose surface increased 4 months later. Initial treatment with 25 mg/d eplerenone resulted in a rapid decrease of subretinal fluid accumulation 1 week later. Eplerenone was then increased to 50 mg/d; a further reduction of the serous detachment was observed 1 week later. Near-complete resolution was observed 3 weeks after the beginning of the treatment. Eplerenone was withdrawn after 5 weeks of administration, and retinal morphology remained normal and stable 5 months after treatment interruption. Scale bar: 200 μm. (B) Fluorescein angiography of the right eye at presentation. The early phase of the angiogram (left) showed multiple RPE disruption white dots (arrows), and leakage at the late phase of the angiogram (right) inducing filling of the subretinal bubble with fluorescein (arrows). Scale bar: 2 mm. (C) Choroidal thickness before and after eplerenone treatment. Other OCT oblique scans focused on deep zones of the eye (choroid vessels): at presentation, choroid vessels were dilated, which was reduced on the same oblique sections of the same zone after 1 and 2 weeks of eplerenone treatment (50 mg/d). Scale bar: 200 μm. Red arrows indicate the orientation and location of the captured image; small arrows delineate the lower limit of the choroid.