Fluorescein angiography, optical coherence tomography, and histopathologic findings in a VEGF165 animal model of retinal angiogenesis

Abstract

To establish an animal model of retinal neovascularization using vascular endothelial growth factor (VEGF165) and analyze the model using optical coherence tomography (OCT), fluorescein angiography (FA), and histopathologic evaluation. Twelve rabbits were divided into groups as follows: group 1 (n = 3), sham intravitreous injections of 0.1ml of balanced saline; group 2 (n = 6), one 10-μg intravitreal injection of VEGF165 on day 0; and group 3 (n = 3), two 10-μg intravitreal injections of VEGF165, one on day 0 and one on day 7. Follow-up evaluations (days 0, 3, 7, 14, 21, 28) included obtaining fundus color photographs and FA, OCT, and histopathologic examinations. Eyes were enucleated and stained with hematoxylin and eosin (H&E). One injection of VEGF (group 2) was associated with dilatation and tortuosity of the retinal blood vessels that developed within 72h. Retinal neovascularization was present by day 7 and regressed by day 14. However, even on day 28, the capillaries were still tortuous. Two VEGF injections (group 3) caused increased leakage and neovascularization up to day 14; severe capillary nonperfusion was seen during week 4. At the end of the follow-up period, OCT and histopathologic examination of group 3 showed peripapillary tractional retinal detachments. By day 7, the differences between the retinal thickness seen on OCT in groups 2 and 3 and the group 1 control group were significant (p < 0.001). The histologic findings showed increased vessel size in groups 2 and 3 by days 14 and 28 compared with the controls. FA, OCT, and histopathologic findings showed that this retinal neovascularization model is efficient, sustainable, and reliable. One injection of VEGF165 created neovascularization that peaked after 1week; two injections created more intense neovascularization that evolved to retinal detachments after 4weeks.