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

PurposeTo 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. MethodsBruch'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 14days by intraperitoneal injection of VS-1 or vehicle (6mice/group). CNV and vascular leakage were measured at three time-points (day 0, 7 and 14) in vivo by spectral domain optical coherence tomography (OCT) and fluorescein angiography (FA). Ex vivo analysis of CNV was also performed at day 14 by confocal microscopy analysis of dextran-perfused choroidal flat-mounts. ResultsIn vivo analyses 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 vivo confocal 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 of in vivo and ex vivo analyses of CNV was also observed (p=0.001, R-2=0.81). ConclusionThe 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.