Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/45279
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
Links: https://www.nature.com/articles/s41467-018-08125-6
http://hdl.handle.net/2381/45279
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 (http://creativecommons.org/licenses/by/4.0/), 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 https://figshare.com/articles/Antagonism_of_the_mineralocorticoid_pathway_limits_choroidal_neovascularization/7283648 . 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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