June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Mineralocorticoid receptor antagonists for the treatment of central serous chorioretinopathy: Mechanistic rationale
Author Affiliations & Notes
  • Francine Behar-Cohen
    Ophthalmology, Hotel Dieu de Paris, Universite Paris Descartes, Paris, France
    UMRS 872 Team 17, Inserm, Paris, France
  • Isabelle Celerier
    UMRS872 Team1, Inserm, Paris, France
  • Elodie Bousquet
    Ophthalmology, Hotel Dieu de Paris, Universite Paris Descartes, Paris, France
    UMRS 872 Team 17, Inserm, Paris, France
  • Jean-Claude Jeanny
    UMRS 872 Team 17, Inserm, Paris, France
  • Frederic Jaisser
    UMRS872 Team1, Inserm, Paris, France
  • Nicolette Farman
    UMRS872 Team1, Inserm, Paris, France
  • Footnotes
    Commercial Relationships Francine Behar-Cohen, Inserm/Univesrité ParisDescartes (P); Isabelle Celerier, None; Elodie Bousquet, None; Jean-Claude Jeanny, None; Frederic Jaisser, None; Nicolette Farman, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 6360. doi:
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      Francine Behar-Cohen, Isabelle Celerier, Elodie Bousquet, Jean-Claude Jeanny, Frederic Jaisser, Nicolette Farman; Mineralocorticoid receptor antagonists for the treatment of central serous chorioretinopathy: Mechanistic rationale. Invest. Ophthalmol. Vis. Sci. 2013;54(15):6360.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: Central serous chorioretinopathy (CSCR) is a vision-threatening eye disease with no validated treatment and unknown pathogeny. Because glucocorticoids induce and aggravate CSCR and can occupy the mineralocorticoid receptor (MR), we investigated whether CSCR may depend on inappropriate MR activation pathway. Our aim was to assess the effect of MR activation on rat choroidal vasculature and to transfer results for patients with CSCR.

Methods: Female Lewis rats (at least 6 animals per conditions) received intravitreous injections (IVT) 5μl of corticosterone (1µM or 10µM final concentration) or aldosterone (20nM final concentration) alone or associated with the MR antagonist potassium canrenoate (10µM final concentration) or with the GR antagonist RU38486 (10µM final concentration). The KCa potassium channel blocker apamin (10µM final concentration) was injected 30 min before sacrifice. The in vivo assessment of rat choroid was performed using spectral domain optical coherence tomography (SD-OCT, Spectralis™ device) and indocyanine green (ICG) angiography (cSLO, HRA). For measurements of protein levels, the RPE-choroid-sclera complex were processed using standard methods for western blotting using rabbit anti-alpha KCa2.3 (1:1000, Alomone Labs). Five patients, presenting with at least 4 months-duration CSCR were treated with oral eplerenone (25mg/ day for a week followed by 50mg/day for a month, after having signed the informed consent. Patients were followed by SD-OCT.

Results: Intravitreous injection of high dose of corticosterone in rat eye induced choroidal enlargement 24 hrs later. The specific MR ligand, aldosterone, elicited the same effect, occurring through specific MR activation, producing choroid vessel dilation and leakage. Aldosterone up-regulates the endothelial vasodilatory potassium channel KCa2.3, exprssed in choroidal endothelial cells, but not in retinal endothelial cells, and its blockade prevents aldosterone-induced thickening. Five patients with long-lasting CRSC (>4 months) were treated with 50mg/day oral eplerenone. This treatment induced a rapid resolution of sub retinal fluid in all cases.

Conclusions: Our results identify MR signaling as a novel pathway controlling choroidal vascular bed relaxation. It provides a pathogenic link between MR pathway activation and human CRSC. We identify MR antagonists as a novel treatment for chronic CSCR.

Keywords: 454 chromatic mechanisms • 451 chorioretinitis • 452 choroid  
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