Downregulation of vascular endothelial growth factor and integrinbeta3 by endostatin in a mouse model of retinal neovascularization.
Retinal neovascularization is among the leading causes of vision impairment throughout the world. Intraocular expression of vascular endothelial growth factor (VEGF), an angiogenic protein, and integrins, a group of cell adhesion molecules, is closely correlated with neovascularization in such neovascular diseases. The purpose of this study is to determine the effect of endostatin, a potent anti-angiogenic factor, on gene expression of vascular endothelial growth factor (VEGF) and integrinbeta3 in a mouse model of oxygen-induced retinopathy. C57BL/6 mice were given intravitreous injections of 1.0 microg endostatin at P12. At P17, retinal VEGF and integrinbeta3 mRNA levels were measured by real-time quantitative PCR in the hyperoxia mice and in the endostatin-treated mice. Analysis of 12 separate experiments revealed a 3.5-fold decrease in VEGF levels between hyperoxia mice and endostatin-treated mice (p<0.01) and a 2.5-fold decrease in integrinbeta3 levels between hyperoxia mice and endostatin-treated mice (p<0.01). These data suggest that intraocular expression of VEGF and integrinbeta3 mRNA is down-regulated by endostatin, which may provide a new therapeutic approach for ocular neovascularization.
Zhang
Meixia
M
West China Eye Center, West China Hospital, Sichuan University, 37 Guoxuexiang, Chengdu, Sichuan Province 610041, China.
Yang
Yang
Y
Yan
Mi
M
Zhang
Junjun
J
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D015536:Down-Regulation; D043169:Endostatins / Q000494:pharmacology*; D005451:Fluorescein Angiography; D039661:Integrin beta3 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D010100:Oxygen; D012333:RNA, Messenger / Q000032:analysis; D012160:Retina / Q000378:metabolism*; D015861:Retinal Neovascularization / Q000378:metabolism* / Q000473:pathology; D012171:Retinal Vessels / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
D020533:Angiogenesis Inhibitors; D043169:Endostatins; D039661:Integrin beta3; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D010100:Oxygen