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

O Konopatskaya, AJ Churchill, Steven J Harper, DO Bates, TA Gardiner

Research output: Contribution to journalArticle (Academic Journal)peer-review

122 Citations (Scopus)

Abstract

Purpose: Hypoxia driven ocular angiogenesis occurs in a range of ischemic retinopathies including proliferative diabetic retinopathy and retinopathy of prematurity. These conditions are initiated and sustained by hypoxia dependent vascular endothelial growth factor (VEGF) expression in the eye. There are two families of VEGF isoforms formed by differential splicing, the pro-angiogenic VEGF family, known to contribute to ocular neovascularization, and the anti-angiogenic VEGF family, which are downregulated in diabetic retinopathy in humans. The first member of the VEGF family to be isolated was VEGF165b. To determine whether VEGF165b could inhibit hypoxia driven angiogenesis in the eye, the oxygen induced retinopathy mouse model of ocular neovascularization was used. Methods: 1 ng of recombinant human VEGF165b peptide was injected intraocularly upon return to normoxia after 5 days exposure to 95% oxygen, and neovascularization assessed. Results: VEGF165b significantly inhibited the percentage area of retinal neovascularization from 23±3% to 12±3.3%, and significantly 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 of VEGF165b can significantly reduce preretinal neovascularization without inhibition of physiological intraretinal angiogenesis. Controlling the balance of VEGFxxx to VEGFxxx isoforms may therefore be therapeutically valuable in the treatment of proliferative eye diseases such as diabetic retinopathy and age related macular degeneration. The regulation of splicing between these two families of isoforms may provide a novel therapeutic strategy for proliferative eye disease.
Translated title of the contributionVEGF165b, an endogenous C-terminal splice variant of VEGF, inhibits retinal neovascularization in mice
Original languageEnglish
Pages (from-to)626 - 632
Number of pages7
JournalMolecular Vision
Volume12
Publication statusPublished - May 2006

Fingerprint Dive into the research topics of 'VEGF<sub>165</sub>b, an endogenous C-terminal splice variant of VEGF, inhibits retinal neovascularization in mice'. Together they form a unique fingerprint.

Cite this