Inhibition of retinal neovascularisation by gene transfer of soluble VEGF receptor sFlt-1

• Published in: Gene therapy Vol. 9; no. 5; pp. 320 - 326
• Main Authors: BAINBRIDGE, J. W. B, MISTRY, A, DE ALWIS, M, PALEOLOG, E, BAKER, A, THRASHER, A. J, ALI, R. R
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.03.2002
• Subjects: Adenoviridae - genetics; Adenoviruses; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Angiogenesis; Animals; Applied cell therapy and gene therapy; Biological and medical sciences; Biotechnology; Blindness; Cornea; Dependovirus - genetics; Endothelial cells; Endothelium; Epithelium; Expression vectors; Extracellular Matrix Proteins - genetics; Fundamental and applied biological sciences. Psychology; Gene Expression; Gene therapy; Gene transfer; Genetic Therapy - methods; Genetic Vectors - administration & dosage; Green fluorescent protein; Health. Pharmaceutical industry; Industrial applications and implications. Economical aspects; Ischemia; Medical sciences; Mice; Mice, Inbred C57BL; Models, Animal; Myosin Heavy Chains; Nonmuscle Myosin Type IIB; Retina; Retinal ganglion cells; Retinal Neovascularization - therapy; Retinopathy; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Vascular endothelial growth factor; Animal model; Adenoviridae; Retinopathy; Rodentia; Retina; Genetic transfer; Virus; Associated virus; Angiogenesis; Eye disease; Vertebrata; Mammalia; Vascular endothelium growth factor; Mouse; Inhibition; Neovascularization; Gene therapy; Biological receptor
• ISSN: 0969-7128; 1476-5462
• DOI: 10.1038/sj.gt.3301680

Retinal angiogenesis is a central feature of the leading causes of blindness. Current treatments for these conditions are of limited efficacy and cause significant adverse effects. In this study, we evaluated the angiostatic effect of gene transfer of the soluble VEGF receptor sFlt-1 in a mouse model of ischaemia-induced retinal neovascularisation using adenovirus and adeno-associated virus (AAV) vectors. We induced proliferative retinopathy in mice by exposure to 75% oxygen from postnatal day 7 (p7) to p12 and injected intravitreally recombinant viral vectors expressing the reporter green fluorescent protein (GFP) or vectors expressing the VEGF inhibitor sFlt-1. Efficient adenovirus-mediated GFP expression was evident in cells of the corneal endothelium and iris pigment epithelium. AAV-mediated GFP expression was evident in ganglion cells and cells of the inner nuclear layer of the retina. Vector-mediated sFlt-1 expression was confirmed by ELISA of pooled homogenised whole eyes. Injection of either vector expressing sFlt-1 resulted in a reduction in the number of neovascular endothelial cells by 56% and 52% for adenovirus and AAV vectors, respectively (P < 0.05). Local gene transfer of sFlt-1 consistently inhibits experimental retinal neovascularisation by approximately 50% and offers a powerful novel approach to the clinical management of retinal neovascular disorders.