In:
Nature Communications, Springer Science and Business Media LLC, Vol. 10, No. 1 ( 2019-01-21)
Kurzfassung:
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.
Materialart:
Online-Ressource
ISSN:
2041-1723
DOI:
10.1038/s41467-018-08125-6
Sprache:
Englisch
Verlag:
Springer Science and Business Media LLC
Publikationsdatum:
2019
ZDB Id:
2553671-0
