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

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.

journal_name

Nat Commun

journal_title

Nature communications

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 MC,Lechner S,Farman N,Bravo-Osuna I,Herrero-Vanrell R,Jaisser F,Behar-Co

doi

10.1038/s41467-018-08125-6

subject

Has Abstract

pub_date

2019-01-21 00:00:00

pages

369

issue

1

issn

2041-1723

pii

10.1038/s41467-018-08125-6

journal_volume

10

pub_type

杂志文章

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