Journal
NATURE COMMUNICATIONS
Volume 10, Issue -, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-018-08125-6
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Funding
- INSERM
- Agence Nationale de la Recherche [ANR Mineraloret ANR-11-BSV1-0022, ROCK-SUR-MeR ANR-15-CE18-0032]
- Swiss National Science Foundation [156260]
- MINECO/AEI/FEDER, UE [MAT2013-43127-R, MAT2017-83858-C2-1]
- Fondation pour la Recherche Medicale (FRM Visual System 2013) [DVS20131228894]
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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.
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