Mineralocorticoid receptor is involved in rat and human ocular chorioretinopathy.
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.
INSERM, U872, Team 17, Centre de Recherche des Cordeliers, Paris, France.
Min
M
Zhao
Isabelle
I
Célérier
Elodie
E
Bousquet
Jean-Claude
JC
Jeanny
Laurent
L
Jonet
Michèle
M
Savoldelli
Olivier
O
Offret
Antoine
A
Curan
Nicolette
N
Farman
Frédéric
F
Jaisser
Francine
F
Behar-Cohen
D000328:Adult; D000450:Aldosterone / Q000494:pharmacology / Q000502:physiology; D000818:Animals; D056833:Central Serous Chorioretinopathy / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D002829:Choroid / Q000098:blood supply; D003345:Corticosterone; D000077545:Eplerenone; D006801:Humans; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D051381:Rats; D018161:Receptors, Mineralocorticoid / Q000378:metabolism*; D012160:Retina / Q000473:pathology; D015398:Signal Transduction; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000235:genetics / Q000378:metabolism; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000627:therapeutic use*; D014792:Visual Acuity / Q000187:drug effects
C496901:Kcnn3 protein, rat; D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid; D051640:Small-Conductance Calcium-Activated Potassium Channels; D014665:Vasodilator Agents; D013148:Spironolactone; D000450:Aldosterone; D000077545:Eplerenone; D003345:Corticosterone