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E.P. Rakoczy, C.–M. Lai, W.–Y. Shen, M. Brankov, N. Barnett, S.–Y. Lee, I. Yeo, C.–L. Ang, M. Degli–Esposti, S. Dunlop; Longevity and Toxicity of AAV–Mediated sFLT–1 Gene Therapy for Ocular Neovascularization in Mice and Monkeys . Invest. Ophthalmol. Vis. Sci. 2006;47(13):833.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the efficacy, longevity and toxicity of adeno–associated virus (AAV)–mediated expression of sFlt–1 in the mouse model of retinal neovascularization (trVEGF029) and in the laser induced monkey model of choroidal neovascularization.
rAAV.sFLT was injected subretinally into trVEGF029 mouse (26) and laser induced monkey (4) eyes. Fluorescence Angiography, histology and immunologycal techniques were used to measure the efficacy, longevity and toxicity of the viral construct.
Transgene expression were to maintained up to 8 and 17 months post–injection in mice and monkeys, respectively. The expression of sFlt–1 was associated with the long–term (8 months) regression of neovascular vessels in 85% of trVEGF029 eyes. The majority of the treated trVEGF029 eyes (75%) retained high numbers of photoreceptors. AAV–mediated expression of sFlt–1 prevented the development of laser photocoagulation–induced choroidal neovascularization in all treated monkey eyes. There were no clinically or histologically detectable signs of toxicity present in either models following AAV.sFlt injection.
These results suggest that AAV–mediated secretion gene therapy could be considered for treatment of retinal and choroidal neovascularization in chronic diseases.
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