Doheny Eye Institute and Department of Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
Graefes Arch Clin Exp Ophthalmol. 2012 Oct;250(10):1421-8. doi: 10.1007/s00417-012-1978-8. Epub 2012 Mar 20.
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 0.1 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).
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.
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.
使用血管内皮生长因子（VEGF165）建立视网膜新生血管动物模型，并通过光相干断层扫描（OCT）、荧光素血管造影（FA）和组织病理学评估分析该模型。
将 12 只兔子分为以下几组：第 1 组（n=3），玻璃体内注射 0.1ml 平衡盐溶液作为假手术对照；第 2 组（n=6），在第 0 天注射 10μg VEGF165；第 3 组（n=3），在第 0 天和第 7 天各注射 10μg VEGF165。在第 0、3、7、14、21 和 28 天进行眼底彩色照相、FA、OCT 和组织病理学检查。眼球取出后行苏木精-伊红（H&E）染色。
单次 VEGF 注射（第 2 组）在 72 小时内导致视网膜血管扩张和迂曲。第 7 天可见视网膜新生血管，第 14 天开始消退。然而，即使在第 28 天，毛细血管仍然迂曲。两次 VEGF 注射（第 3 组）导致第 14 天新生血管化加剧和渗漏增加；第 4 周可见严重的毛细血管无灌注。在随访期末，第 3 组的 OCT 和组织病理学检查显示视盘周围牵拉性视网膜脱离。第 7 天，第 2 组和第 3 组与对照组的 OCT 视网膜厚度差异有统计学意义（p<0.001）。第 14 天和第 28 天，第 2 组和第 3 组的组织学发现血管大小增加。
FA、OCT 和组织病理学检查结果表明，该视网膜新生血管模型有效、可持续且可靠。单次 VEGF165 注射可在 1 周内引起新生血管形成，达到高峰；两次注射可引起更强烈的新生血管形成，4 周后发展为视网膜脱离。
