Gefitinib inhibits retina angiogenesis by affecting VEGF signaling pathway

Abstract

Gefitinib, a small-molecule multitargeted tyrosine kinase inhibitor, is reported to be as a new oral antiangiogenic molecule. However, it is unknown whether Gefitinib inhibits retina angiogenesis. In this study, we aimed to investigate the effect of Gefitinib on oxygen-induced retinal angiogenesis and the correlation between Gefitinib and VEGF signaling pathway. 12 cases of mice models of oxygen-induced retinopathy were obtained by exposing to 75% oxygen for 7 days. Then, these models were randomly assigned to two groups, and treated with Gefitinib and DMSO, respectively. Retinal vascular morphology was evaluated by Ink staining, HE staining and isolectin staining. Finally, the expression levels of VEGF, Cyclin E, CDK2, CD31 were detected in retinal tissues. Results shown that newborn retinal vessels and oxygen-induced vaso-obliteration were easily to be observed in oxygen-induced groups compared with controls. Meanwhile, the number of nonganglion cells and neovascular nuclei in oxygen-induced groups was significantly increased compared with those in control groups. However, when treated with Gefitinib, newborn retinal vessels in mice models of oxygen-induced retinopathy were significantly reduced. Further investigation confirmed that Gefitinib treatment affected the VEGF/Cyclin E/CDK2/CD31 pathway. In conclusion, these findings indicate that Gefitinib is critical for the treatment of retina angiogenesis, which is associated with VEGF/Cyclin E/CDK2/CD31 pathway.