May 2006
Volume 47, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2006
Intravitreal Injection of siRNA Targeting VEGF Inhibits Retinal Neovascularization in a Mouse Model of Retinopathy
Author Affiliations & Notes
  • M. Zhang
    West China Eye Center, West China Hospital, Chengdu, China
  • J. Zhang
    West China Eye Center, West China Hospital, Chengdu, China
  • B. Guo
    West China Eye Center, West China Hospital, Chengdu, China
    Engineering Research Center in Biomaterials, Sichuan University, China
  • Y. Liu
    West China Eye Center, West China Hospital, Chengdu, China
  • F. Lu
    West China Eye Center, West China Hospital, Chengdu, China
    Yale Eye Center, Yale University School of Medicine, CT
  • M. Yan
    West China Eye Center, West China Hospital, Chengdu, China
  • M. Zhang
    West China Eye Center, West China Hospital, Chengdu, China
  • L. Ma
    West China Eye Center, West China Hospital, Chengdu, China
  • Footnotes
    Commercial Relationships  M. Zhang, None; J. Zhang, None; B. Guo, None; Y. Liu, None; F. Lu, None; M. Yan, None; M. Zhang, None; L. Ma, None.
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science May 2006, Vol.47, 841. doi:
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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)

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Abstract

Purpose: : To investigate the effect of the small interfering RNA (siRNA) directed against vascular endothelial growth factor in a mouse model of oxygen–induced retinopathy.

Methods: : 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.

Results: : 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.

Conclusions: : 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.

Keywords: gene transfer/gene therapy • retinal neovascularization 
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