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O. Konopatskaya, S.J. Harper, A.J. Churchill, D.O. Bates, T.A. Gardiner; VEGF165b, an Endogenous C–Terminal Splice Variant of VEGF, Inhibits Retinal Neovascularisation in Mice . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1749.
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Vascular Endothelial Growth Factor–A (VEGF–A) is a key stimulator of pathological retinal neovascularisation in such diseases as diabetic retinopathy, age–related macular degeneration and retinopathy of prematurity. VEGF–A is alternatively spliced to form a potentially anti–angiogenic family of isoforms (VEGFxxxb), which are expressed in normal human tissues, including eye tissues, and downregulated in renal and prostate cancer. Since VEGF165b has previously been shown to inhibit VEGF165–dependent angiogenesis in vivo (J.Woolard et al, Cancer Res. 2004 64: 7822–35), we set out to determine the effect of VEGF165b in the murine model of oxygen–induced retinopathy.
From postnatal day 7 (P7) on, C57/BL6 mice (total 33) were kept in 75% oxygen environment for 5 days. On postnatal day 13 (P13) neonates were divided in 2 groups, one being injected intraocularly with human recombinant VEGF165b (1µl at 1ng/ml) and the other as a control group was treated with vehicle (PBS) alone. On P17 retinal flatmounts were prepared and the extent of ischaemic retinopathy was evaluated using NIH image software.
Exposure of mice to hyperoxia for 5 days followed by normoxia resulted in formation of substantial ischaemic (15±1.4%) and neovascularised (23±3%) areas. Administration of VEGF165b did not affect the ischaemic region, but caused significant reduction in the neovascularisation to 12±3.3% (p<0.05, Wilcoxon paired test).
These results demonstrate that the alternatively spliced variant of VEGF, VEGF165b, is an effective inhibitor of ischaemia–induced retinal neovascularisation in vivo, and may offer a novel therapeutic strategy to prevent or treat neovascular ocular diseases.
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