Antagonism of the mineralocorticoid pathway limits choroidal neovascularization

Choroidal neovascularization (CNV) is a major cause of visual impairment in wet age-related macular degeneration (AMD) patients, particularly when refractory to intraocular anti-VEGF injections. Here we report that co-treatment with the oral mineralocorticoid receptor (MR) antagonist, spironolactone reduces signs of CNV in refractory cases. In a model of wet AMD, MR pathway inhibition with pharmacological or conditional transgenic approaches inhibits CNV development through VEGF-independent mechanisms at least partially mediated by the extracellular matrix protein, decorin. Slowly released local spironolactone is as efficient as systemic treatment, opening up novel therapeutic avenues for neovascular AMD unresponsive to anti-VEGF drugs.