Induction of Choroidal Neovascularization by Sustained Release of VEGF/Bfgf in Rabbits: Angiographic Characterization and Histologic Correlation on Different Patterns of the Choroidal Vascular Response

Abstract

Abstract: : Purpose: Previous studies demonstrate the induction of florid choroidal neovascularization (CNV) from sustained release of both VEGF and bFGF within the suprachoroidal space of the pigmented rabbit (Carvalho and Wong, 2001). This study aims to demonstrate the CNV response to different doses of growth factors and to characterize further the in vivo progression of the CNV. Methods: Dutch Belted rabbits (N = 21) were divided into 3 groups with N = 7 per group. Negative controls were implanted transclerally in the right eye with blank Hydron pellets within the suprachoroidal space; a second group received 7.5ug VEGF/10 ug bFGF–containing pellets, while a third group received 15 ug VEGF/20 ug bFGF–containing pellets. Development of CNV was monitored and assessed by color fundus photography and fluorescein angiography at 1,2,3,4, and 8 weeks after the implant procedures. At either 4 or 8 weeks, animals were euthanized; and histology was performed on the enucleated eyes. Results: CNV was detected by fluorescein angiography in all eyes that were exposed to both VEGF and bFGF. Initial choroidal changes include vascular dilation, which could be observed at week 1 around the pellet implantation site. The CNV response consisted of two types: polypoidal–like lesions and fan–like patterns. Development of the neovascular lesion progressed up to week 3; and the fan–like lesions were still present by week 8. Moreover, retinal vascular changes could be observed mainly in the high dose group.Conclusions: Different levels of the growth factors produced a florid CNV response in the rabbit eye. Induction of a long–lasting choroidal neovascular lesion can provide a practical experimental CNV model for standardized testing of promising therapeutics against exudative aging–related macular degeneration. The different patterns of CNV can resemble different stages of the disease in humans, particularly before overt growth of the CNV into the subretinal space.

Keywords: neovascularization • age-related macular degeneration • retinal neovascularization