Rac1 activates HIF-1 in laser induced choroidal neovascularization

Int J Ophthalmol. 2011;4(1):14-8. doi: 10.3980/j.issn.2222-3959.2011.01.03. Epub 2011 Feb 18.

Abstract

Aim: To study the effect of Rac1 on the induction of HIF-1α in choroidal neovascularization (CNV) in mice.

Methods: 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.

Results: 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.

Conclusion: Rac1 is crucial to activate HIF-1 regulating the growth of CNV, and its inhibition may have potential therapeutic value.

Keywords: animal study; choroidal neovascularisation; growth factor; molecular biology; signal transduction.