Pathologic feature of vacular endothelial growth factor-induced retinopathy in the nonhuman primate

PURPOE: Vacular endothelial growth factor (VEGF) i a potent ichemia-upregulated angiogenic protein that ha been implicated in diabetic retinopathy. Intravitreal VEGF injection have not previouly been hown to produce preretinal neovacularization. The purpoe of thi tudy wa to further characterize the angiopathic change that occur after intravitreal injection in a nonhuman primate and determine if preretinal neovacularization develop. DEIGN: Experimental animal tudy. METHOD: Vacular endothelial growth factor 165 wa injected into the eye of normal cynomolgu monkey at regular interval. A a control, normal eye were injected with phophate buffered aline. Color photography and fluorecein angiography were performed at regular interval. The retina were incubated for adenoine diphophatae (ADPae) activity to viualize retinal veel. The retina were flat-embedded and area of potential preretinal neovacularization were identified en bloc and erially ectioned. REULT: Area of capillary nonperfuion and veel dilation and tortuouity were een by angiography. In erial ection, the nonperfued area were found to be aociated with endothelial cell hyperplaia in veel lumen. Preretinal neovacularization originating only from uperficial vein and venule wa oberved throughout peripheral retina, but wa not een in the poterior pole. Lacunae-like vein were ubdivided by the proce of intuuception and endothelial cell bridging. Arteriole demontrated endothelial cell hyperplaia and microaneurym. CONCLUION: Intraocular injection of VEGF were ufficient to produce preretinal neovacularization in the nonhuman primate. Mot vaculopathic tructure were aociated with endothelial cell hyperplaia. Thee reult demontrate that VEGF alone can produce many feature of both nonproliferative and proliferative diabetic retinopathy including the previouly undecribed development of preretinal neovacularization. Thi well-characterized VEGF-induced primate model of retinal neovacularization may be ueful a a mean of teting new treatment for retinal neovacularization.