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Q. Li, R. Miller, J. Pang, S. Boye, V. Choido, A. Scaria, P. Pechan, H. Rubin, S. Wadsworth, W. Hauswirth; A Novel Recombinant Form of VEGF Soluble Receptor 1 (sFlt–1) Delivered via AAV Vectors Effectively Inhibits Choroidal Neovascularization in a Murine Model . Invest. Ophthalmol. Vis. Sci. 2006;47(13):901.
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© ARVO (1962-2015); The Authors (2016-present)
Choroidal neovascularization (CNV) occurs in variety of chorioretinal diseases, including age–related macular degeneration (AMD) and is the major cause of severe visual loss in patients with AMD. VEGF is known to be a critical stimulus for CNV. In this study, we investigated the feasibility of using a novel genetically engineered soluble form of VEGF receptor 1 (sFlt–1) as a therapeutic agent for treating choroidal neovascularization in an experimental animal model.
Materials and Methods: :
A cDNA for a genetically engineered soluble form of Flt–1 was packaged into an AAV serotype 2 vector under control of the chicken ß–actin/CMV enhancer promoter (CBA). The vector was injected intravitreously into the right eyes of adult C57BL/6 mice. 532nm laser photocoagulation was performed 4–8 weeks after injection to focally rupture Bruch’s membrane in both eyes (4–5 sites each eye). The development of CNV at each laser burn was evaluated 14 days later by fluorescein angiographic choroidal flat–mount image analysis, as well as by histology of transverse retinal sections.
Treatment with AAV2– CBA–sFlt–1 significantly reduced both the incidence of laser–induced CNV and the average area of CNV at sites of the Bruch’s membrane rupture. Two weeks after laser photocoagulation, 145 of 179 burns (81%) in control eyes (n=38) developed extensive CNV, whereas in treated eyes (n=30), only 58 of 150 burns (38.67%) eyes developed CNV. These results were derived from injection of three different AAV vector preparations. The size of CNV area was also significantly decreased (∼73% reduction) in treated eyes compared to untreated control eyes. Eyes treated with an analogous vector containing an inactive form of the sFlt–1 agent were essentially indistinguishable from control eyes.
These results demonstrate that the sFlt–1 construct delivered via AAV vector is a promising candidate for treatment of the CNV seen in patients with the exudative form of AMD and may be extended to other chorioretinal diseases with CNV as well.
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