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M. Zhang, J. Zhang, B. Guo, Y. Liu, F. Lu, M. Yan, M. Zhang, L. Ma; Intravitreal Injection of siRNA Targeting VEGF Inhibits Retinal Neovascularization in a Mouse Model of Retinopathy . Invest. Ophthalmol. Vis. Sci. 2006;47(13):841.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the effect of the small interfering RNA (siRNA) directed against vascular endothelial growth factor in a mouse model of oxygen–induced retinopathy.
A siRNA double expression vector of pU–VEGF–siRNA /pCMV –GFP was conducted. We induced retinopathy by exposing 7–day–old mice to high levels of oxygen. Intravitreally injected the vector in the left eyes, and the pCMV–GFP vector in the right eyes as control. The level of VEGF was determined by Western blot, real–time quantitative PCR and immunohistochemistry. The retinal vascular structure was studied through fluorescein–isothiocyanate–dextran angiography and retinal flat mount. The total number of the neovascular tufts were analyzed by histological sections.
The double expression vector of pU–VEGF–siRNA /pCMV –GFP successfully delivered to the retina. Compared to the controls, quantitative RT–PCR demonstrated statistically significant reduction of 87% in VEGF mRNA after intravitreous injection of pU–VEGF–siRNA /pCMV –GFP. Retinal flat mount indicated a single administration of VEGF siRNA could significantly inhibite the growth of retinal neovacularization. The number of neovascular tufts was lower in pU–VEGF–siRNA /pCMV –GFP –injected eyes (p = 0.0001) than controls.
These data suggest that VEGF plays an important role in the development of retinal neovascularization. Intravitreal injection of siRNA targeting VEGF mRNA may provide an effective tool for ocular neovascular diseases.
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