Inducible Expression of VEGF After Rupture of Bruch’s Membrane Causes Severe Choroidal Neovascularization; Contribution of VEGF Receptor 1

Abstract

Purpose: : Increased expression of vascular endothelial growth factor (VEGF) in photoreceptors is sufficient to stimulate sprouting of neovascularization from the deep capillary bed of the retina, but not from the superficial retinal capillaries or the choriocapillaris. In this study, we used double transgenic mice with inducible expression of VEGF in the retina (Tet/IRBP/VEGF transgenic mice) to investigate the effect of increased expression of VEGF after laser-induced rupture of Bruch’s membrane on the area of choroidal neovascularization (CNV).

Methods: : Adult Tet/IRBP/VEGF mice were given low dose (0.5mg/mL) or high dose (2mg/mL) doxycycline treatment after rupture of Bruch’s membrane. The area of CNV was measured on day 7 by histological examination and image analysis of choroidal flat mounts from mice perfused with fluorescein-labeled dextran.

Results: : Compared to untreated Tet/IRBP/VEGF mice, those treated with high dose doxycycline treatment, but not those treated with lose dose doxycycline, had significantly larger CNV lesions, and this was blocked by intraocular injection of an antibody directed against VEGF receptor 1.

Conclusions: : These data indicate that continuous increased expression of VEGF markedly stimulates the growth of CNV after rupture of Bruch’s membrane and this proangiogenic effect is mediated in part by VEGF receptor 1.

Keywords: choroid: neovascularization • vascular endothelial growth factor • transgenics/knock-outs