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.

脉络膜新生血管（Choroidal Neovascularization, CNV）是湿性年龄相关性黄斑变性（wet age-related macular degeneration, AMD）患者视力损害的主要病因，当患者对眼内抗血管内皮生长因子（anti-Vascular Endothelial Growth Factor, anti-VEGF）注射治疗产生耐药时，该病症尤为难治。本研究表明，联合口服盐皮质激素受体（Mineralocorticoid Receptor, MR）拮抗剂螺内酯，可减轻耐药性CNV病例的病情体征。在湿性AMD模型中，通过药理学手段或条件性转基因方法抑制MR通路，可通过不依赖VEGF的机制阻断CNV的发生发展，该效应部分由细胞外基质蛋白核心蛋白聚糖（Decorin）介导。局部缓释型螺内酯的疗效与全身给药相当，为抗VEGF药物应答不佳的新生血管性AMD患者开辟了全新的治疗途径。