Mineralocorticoid receptor antagonism limits experimental choroidal neovascularization and structural changes associated with neovascular age-related macular degeneration

Min Zhao, Irmela Mantel, Emmanuelle Gelize, Xinxin Li, Xiaoyue Xie, Alejandro Arboleda, Marie Seminel, Rinath Levy-Boukris, Marilyn Dernigoghossian, Andrea Prunotto, Charlotte Andrieu-Soler, Carlo Rivolta, Jérémie Canonica, Marie-Christine Naud, Sebastian Lechner, Nicolette Farman, Irene Bravo-Osuna, Rocio Herrero-Vanrell, Frederic Jaisser and Francine Behar-Cohen ()
Additional contact information
Min Zhao: Inserm UMR_S 1138, Team 17, Centre de Recherche des Cordeliers
Irmela Mantel: University of Lausanne, Jules Gonin Eye Hospital, Fondation Asile des Aveugles
Emmanuelle Gelize: Inserm UMR_S 1138, Team 17, Centre de Recherche des Cordeliers
Xinxin Li: Inserm UMR_S 1138, Team 17, Centre de Recherche des Cordeliers
Xiaoyue Xie: Inserm UMR_S 1138, Team 17, Centre de Recherche des Cordeliers
Alejandro Arboleda: Inserm UMR_S 1138, Team 17, Centre de Recherche des Cordeliers
Marie Seminel: Inserm UMR_S 1138, Team 17, Centre de Recherche des Cordeliers
Rinath Levy-Boukris: Inserm UMR_S 1138, Team 17, Centre de Recherche des Cordeliers
Marilyn Dernigoghossian: Inserm UMR_S 1138, Team 17, Centre de Recherche des Cordeliers
Andrea Prunotto: University of Lausanne
Charlotte Andrieu-Soler: IGMM, CNRS, Univ. Montpellier
Carlo Rivolta: University of Lausanne
Jérémie Canonica: University of Lausanne, Jules Gonin Eye Hospital, Fondation Asile des Aveugles
Marie-Christine Naud: Inserm UMR_S 1138, Team 17, Centre de Recherche des Cordeliers
Sebastian Lechner: Sorbonne University, University of Pierre et Marie Curie, UMR_S 1138, Centre de Recherche des Cordeliers
Nicolette Farman: Sorbonne University, University of Pierre et Marie Curie, UMR_S 1138, Centre de Recherche des Cordeliers
Irene Bravo-Osuna: Universidad Complutense de Madrid
Rocio Herrero-Vanrell: Universidad Complutense de Madrid
Frederic Jaisser: Sorbonne University, University of Pierre et Marie Curie, UMR_S 1138, Centre de Recherche des Cordeliers
Francine Behar-Cohen: Inserm UMR_S 1138, Team 17, Centre de Recherche des Cordeliers

Nature Communications, 2019, vol. 10, issue 1, 1-13

Abstract: Abstract Choroidal neovascularization (CNV) is a major cause of visual impairment in patients suffering from wet age-related macular degeneration (AMD), particularly when refractory to intraocular anti-VEGF injections. Here we report that treatment with the oral mineralocorticoid receptor (MR) antagonist spironolactone reduces signs of CNV in patients refractory to anti-VEGF treatment. In animal models of wet AMD, pharmacological inhibition of the MR pathway or endothelial-specific deletion of MR inhibits CNV through VEGF-independent mechanisms, in part through upregulation of the extracellular matrix protein decorin. Intravitreal injections of spironolactone-loaded microspheres and systemic delivery lead to similar reductions in CNV. Together, our work suggests MR inhibition as a novel therapeutic option for wet AMD patients unresponsive to anti-VEGF drugs.

Date: 2019
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DOI: 10.1038/s41467-018-08125-6

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