VEGF165b, an endogenous C-terminal splice variant of VEGF,inhibits retinal neovascularization in mice

[摘要] Purpose: Hypoxia driven ocular angiogenesis occurs in a range ofischemic retinopathies including proliferative diabetic retinopathy andretinopathy of prematurity. These conditions are initiated and sustainedby hypoxia dependent vascular endothelial growth factor (VEGF)expression in the eye. There are two families of VEGF isoforms formed bydifferential splicing, the pro-angiogenic VEGF family, known tocontribute to ocular neovascularization, and the anti-angiogenic VEGFfamily, which are downregulated in diabetic retinopathy in humans. Thefirst member of the VEGF family to be isolated was VEGF165b. Todetermine whether VEGF165b could inhibit hypoxia drivenangiogenesis in the eye, the oxygen induced retinopathy mouse model ofocular neovascularization was used.Methods: 1 ng of recombinant human VEGF165b peptide wasinjected intraocularly upon return to normoxia after 5 days exposure to95% oxygen, and neovascularization assessed.Results: VEGF165b significantly inhibited the percentage areaof retinal neovascularization from 23±3% to 12±3.3%, andsignificantly increased normal vascular areas from 62±4% to 74±4%. The percentage area of residual ischemic retina was not affected.Conclusions: These results show that a single injection ofVEGF165b can significantly reduce preretinal neovascularizationwithout inhibition of physiological intraretinal angiogenesis.Controlling the balance of VEGFxxx to VEGFxxx isoforms maytherefore be therapeutically valuable in the treatment of proliferativeeye diseases such as diabetic retinopathy and age related maculardegeneration. The regulation of splicing between these two families ofisoforms may provide a novel therapeutic strategy for proliferative eyedisease.

[学科分类] 生物化学/生物物理