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Title: Mineralocorticoid receptor antagonism limits experimental choroidal neovascularization and structural changes associated with neovascular age-related macular degeneration.
Authors: Zhao, M
Mantel, I
Gelize, E
Li, X
Xie, X
Arboleda, A
Seminel, M
Levy-Boukris, R
Dernigoghossian, M
Prunotto, A
Andrieu-Soler, C
Rivolta, C
Canonica, J
Naud, M-C
Lechner, S
Farman, N
Bravo-Osuna, I
Herrero-Vanrell, R
Jaisser, F
Behar-Cohen, F
First Published: 21-Jan-2019
Publisher: Nature Research (part of Springer Nature)
Citation: Nature Communications, 2019, volume 10, Article number: 369
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.
DOI Link: 10.1038/s41467-018-08125-6
eISSN: 2041-1723
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © the authors, 2019. This is an open-access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Description: All relevant data are available from the corresponding author upon reasonable request. RNA-sequencing data are available from ArrayExpress database at EMBL-EBI under accession number E-MTAB-7438. The images from figures are available at figshare . A Reporting Summary for this Article is available as a Supplementary Information file.
Appears in Collections:Published Articles, Dept. of Genetics

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