Hua, J and Spee, C and Kase, S and Rennel, ES and Magnussen, AL and Qiu, Y and Varey, A and Dhayade, S and Churchill, AJ and Harper, SJ and Bates, DO and Hinton, DR (2010) Recombinant Human VEGF(165)b Inhibits Experimental Choroidal Neovascularization. INVEST OPHTH VIS SCI , 51 (8) 4282 - 4288. 10.1167/iovs.09-4360.
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PURPOSE. Vascular endothelial growth factor (VEGF-A) is the principal stimulator of angiogenesis in wet age-related macular degeneration (AMD). However, VEGF-A is generated by alternate splicing into two families, the proangiogenic VEGF-A(xxx) family and the antiangiogenic VEGF-A(xxx)b family. It is the proangiogenic family that is responsible for the blood vessel growth seen in AMD.METHODS. To determine the role of antiangiogenic isoforms of VEGF-A as inhibitors of choroidal neovascularization, the authors used a model of laser-induced choroidal neovascularization in the mouse eye and investigated VEGF-A(165)b effects on endothelial cells and VEGFRs in vitro.RESULTS. VEGF-A(165)b inhibited VEGF-A(165)-mediated endothelial cell migration with a dose effect similar to that of ranibizumab and bevacizumab and 200-fold more potent than that of pegaptanib. VEGF-A(165)b bound both VEGFR1 and VEGFR2 with affinity similar to that of VEGF-A(165). After laser injury, mice were injected either intraocularly or subcutaneously with recombinant human VEGF-A(165)b. Intraocular injection of rhVEGF-A(165)b gave a pronounced dose-dependent inhibition of fluorescein leakage, with an IC50 of 16 pg/eye, neovascularization (IC50, 0.8 pg/eye), and lesion as assessed by histologic staining (IC50, 8 pg/eye). Subcutaneous administration of 100 mu g twice a week also inhibited fluorescein leakage and neovascularization and reduced lesion size.CONCLUSIONS. These results show that VEGF-A(165)b is a potent antiangiogenic agent in a mouse model of age-related macular degeneration and suggest that increasing the ratio of antiangiogenic-to-proangiogenic isoforms may be therapeutically effective in this condition. (Invest Ophthalmol Vis Sci. 2010; 51:4282-4288) DOI:10.1167/iovs.09-4360
|Title:||Recombinant Human VEGF(165)b Inhibits Experimental Choroidal Neovascularization|
|Keywords:||ENDOTHELIAL GROWTH-FACTOR, MACULAR DEGENERATION, SPLICE VARIANT, DIABETIC-RETINOPATHY, ANGIOGENIC ISOFORMS, VEGF, EXPRESSION, PERMEABILITY, THERAPY, RANIBIZUMAB|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Wolfson Institute and Cancer Institute Administration > Cancer Institute > Research Department of Oncology|
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