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

Arana, Luís; Pinto, Anderson; Chader, Gerald; Barbosa, Jose; Morales, Sabina; Moreira, Ana; Maia, Mauricio; Humayun, Mark
October 2012
Graefe's Archive of Clinical & Experimental Ophthalmology;Oct2012, Vol. 250 Issue 10, p1421
Academic Journal
Background: 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. Methods: Twelve rabbits were divided into groups as follows: group 1 ( n = 3), sham intravitreous injections of 0.1 ml 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). Results: One injection of VEGF (group 2) was associated with dilatation and tortuosity of the retinal blood vessels that developed within 72 h. 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. Conclusions: 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 1 week; two injections created more intense neovascularization that evolved to retinal detachments after 4 weeks.


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