Zhang Peng, Zhang Xing, Fan Jiang-Li, Hao Xiao-Feng, Wang Yu-Sheng, Hui Yan-Nian, Hu Dan, Zhou Jian
Department of Ophthalmology, Xijing Hospital, Fourth Military Medical University, Xi'an710032, Shaanxi Province, China.
Int J Ophthalmol. 2011;4(1):14-8. doi: 10.3980/j.issn.2222-3959.2011.01.03. Epub 2011 Feb 18.
To study the effect of Rac1 on the induction of HIF-1α in choroidal neovascularization (CNV) in mice.
One hundred C57BL/6J mice were laser photocoagulated to induce CNV, fifty mice of that were selected randomly for intravitreal injection of Rac1 inhibitor NSC23766 solution (1µL). After laser photocoagulation, fundus fluorescein angiography (FFA) was performed to verify the growth of CNV, Immunohistochemistry and Western blot were used to detect HIF-1α and Rac1 in posterior segment of eye globes.
FFA verified that incidence of CNV was significantly reduced in the eyes with NSC23766 injection comparing with that of eyes without NSC23766 injection (P<0.01). Immunohistochemistry detected that HIF-1α and Rac1 mainly expressing in the new fibrovascular tissue. Western blot showed that HIF-1α and Rac1 was highly increased in tissue explants of retinal pigment epithelium (RPE) and choroid without NSC23766 injection. But for tissue explants of RPE and choroid with NSC23766 injection, both the expression of HIF-1α and Rac1 were inhibited.
Rac1 is crucial to activate HIF-1 regulating the growth of CNV, and its inhibition may have potential therapeutic value.
研究Rac1对小鼠脉络膜新生血管（CNV）中低氧诱导因子-1α（HIF-1α）诱导作用的影响。
将100只C57BL/6J小鼠进行激光光凝诱导CNV，从中随机选取50只小鼠玻璃体内注射Rac1抑制剂NSC23766溶液（1μL）。激光光凝后，行眼底荧光血管造影（FFA）以验证CNV的生长情况，采用免疫组织化学和蛋白质印迹法检测眼球后段的HIF-1α和Rac1。
FFA证实，注射NSC23766的眼睛中CNV的发生率较未注射NSC23766的眼睛显著降低（P<0.01）。免疫组织化学检测发现HIF-1α和Rac1主要表达于新生纤维血管组织中。蛋白质印迹法显示，未注射NSC23766的视网膜色素上皮（RPE）和脉络膜组织外植体中HIF-1α和Rac1高度升高。但对于注射了NSC23766的RPE和脉络膜组织外植体，HIF-1α和Rac1的表达均受到抑制。
Rac1对激活HIF-1调节CNV生长至关重要，抑制其表达可能具有潜在的治疗价值。
