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.