Effect of chromogranin A-derived vasostatin-1 on laser-induced choroidal neovascularization in the mouse

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ABSTRACT.Purpose:To verify the effect of vasostatin-1 (VS-1), an anti-angiogenic fragment of chromogranin A, in the prevention of choroidal neovascularization (CNV) in an established mouse model of laser-induced ocular neovascularization.Methods:Bruch's membrane, the innermost layer of the choroid, was broken by laser photocoagulation in C57/Bl6 mice, to induce CNV. Mice were then treated daily for 14 days by intraperitoneal injection of VS-1 or vehicle (6 mice/group). CNV and vascular leakage were measured at three time-points (day 0, 7 and 14)in vivoby spectral domain optical coherence tomography (OCT) and fluorescein angiography (FA).Ex vivoanalysis of CNV was also performed at day 14 by confocal microscopy analysis of dextran-perfused choroidal flat-mounts.Results:In vivoanalyses showed that VS-1 significantly reduced CNV at day 14 (p = 0.03) and vascular leakage at day 7 (p = 0.01) and 14 (p = 0.04).Ex vivoconfocal microscopy analysis of CNV performed on dextran-perfused choroidal flat-mounts at day 14 confirmed the protective activity of VS-1 (p = 0.01). A significant correlation between the results ofin vivoandex vivoanalyses of CNV was also observed (p = 0.001,R2 = 0.81).Conclusion:The results indicate that VS-1 can prevent CNV and vascular leakage in a mouse model of ocular neovascularization, suggesting that this polypeptide might have therapeutic activity in human ocular diseases that are complicated by neovascularization or excessive vascular permeability.

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