Inhibition of choroidal neovascularization by topical application of angiogenesis inhibitor vasostatin

[摘要] Purpose: Choroidal neovascularization(CNV) is the leading cause of blindness in patients with age-relatedmacular degeneration (AMD). This study evaluated the inhibitory effectof vasostatin (VS), an endogenous angiogenesis inhibitor, on CNV. Methods: Anti-angiogenic activity of VSwas evaluated in vitro by migration and tube formation assays in humanumbilical vein endothelial cells (HUVECs). CNV lesions were induced inBrown Norway rats by fundus argon laser photocoagulation. Beginning oneday after CNV induction, rats were treated with eye drops containing 1μg/ml VS in PBS buffer for three times daily for 20 days. The extent ofCNV was examined by flat mount analysis on day 24 or by fundusfluorescein angiography (FAG) on days 21, 28, 35, and 42, respectively.CNV lesions and choroidal vascularity were evaluated by histologicalanalysis. The spatial distribution of topically applied VS in rat eyeswas evaluated by immunoblot analysis. Results: VS inhibited migration and tubeformation in HUVECs. Flat mount analysis revealed that, afterlaser-induced photocoagulation, topical VS application for 20 dayssignificantly reduced CNV lesions. Moreover, serial FAG analysisindicated that a 20 day VS treatment significantly reduced CNV lesionson all subsequent days. Histological analysis revealed attenuatedlesions, intact Bruch’s membrane, and reduced choroidal vascularity inVS-treated eyes. Finally immunoblot analysis reveled VS expression inchoroids. Conclusions: Topical VS applicationsuppresses the progression of laser-induced CNV via angiogenesisinhibition and may constitute a therapeutic alternative for excessiveneovascularization occurring with ocular diseases.

[学科分类] 生物化学/生物物理