May 2003
Volume 44, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2003
VEGF Directed siRNA Inhibits Experimental Choroidal Neovascularization
S.J. Reich; A. Kuroki; J. Fosnot; X.Y. Yang; A.M. Maguire; J. Bennett; M.J. Tolentino
Author Affiliations & Notes
  • S.J. Reich
    Department of Ophthalmology, University of Pennsylvania, FM Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, Philadelphia, PA, United States
  • A. Kuroki
    Department of Ophthalmology, University of Pennsylvania, FM Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, Philadelphia, PA, United States
  • J. Fosnot
    Department of Ophthalmology, University of Pennsylvania, FM Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, Philadelphia, PA, United States
  • X.Y. Yang
    Department of Ophthalmology, University of Pennsylvania, FM Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, Philadelphia, PA, United States
  • A.M. Maguire
    Department of Ophthalmology, University of Pennsylvania, FM Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, Philadelphia, PA, United States
  • J. Bennett
    Department of Ophthalmology, University of Pennsylvania, FM Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, Philadelphia, PA, United States
  • M.J. Tolentino
    Department of Ophthalmology, University of Pennsylvania, FM Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, Philadelphia, PA, United States
  • Footnotes
    Commercial Relationships  S.J. Reich, None; A. Kuroki, None; J. Fosnot, None; X.Y. Yang, None; A.M. Maguire, None; J. Bennett, None; M.J. Tolentino, None.
  • Footnotes
    Support  RPB, NIH grants EY-13410 and EY12156, JDRF, Steinbach Foundation, FM Kirby Foundation
Investigative Ophthalmology & Visual Science May 2003, Vol.44, 578. doi:
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      S.J. Reich, A. Kuroki, J. Fosnot, X.Y. Yang, A.M. Maguire, J. Bennett, M.J. Tolentino; VEGF Directed siRNA Inhibits Experimental Choroidal Neovascularization . Invest. Ophthalmol. Vis. Sci. 2003;44(13):578.

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Abstract

Abstract: : Purpose: Gene silencing of angiogenic factors involved in pathologic neovascularization may be an important therapeutic anti-angiogenic strategy. The purpose of this study is to determine if murine vascular endothelial growth factor (VEGF)-directed siRNA will inhibit experimental laser induced choroidal neovascularization (CNV) in mice. Methods:Adult female C57BL/6 mice were laser photocoagulated using an 810 nm diode laser (OcuLight Six; IRIS Medical, Mountain View, CA). Three laser spots were applied in both eyes. One day post-treatment, subretinal injections were performed unilaterally to deliver siRNA that targets mouse VEGF. The siRNA was conjugated with transit TKO transfection reagent (Mirus) and mixed with recombinant adenovirus (rAdenovirus). Contralateral eyes received subretinal injections of siRNA targeting GFP and served as controls. This siRNA was also conjugated with transit TKO reagent (Mirus) and mixed with rAdenovirus. Two weeks following laser treatment, animals were perfused with high molecular weight FITC-Dextran, and choroidal flat mounts were prepared. Choroidal flat mounts were photographed and analyzed microscopically. The area of CNV was measured with Openlab software (Improvision, Boston, MA). Results: Eyes treated with VEGF directed siRNA showed a statistically significant decrease in the size of the choroidal neovasculariation as compared with the control eye. Average CNV area in eyes treated with siRNA directed to GFP was 0.08 mm2. In the murine VEGF directed siRNA treated eyes average CNV area was 0.03. mm 2. The difference was statistically significant ( p< 0.00004). Conclusion: Gene silencing with siRNA directed towards VEGF can significantly inhibit neovascularization in the murine laser induced CNV model. This experiment helps validate the strategy of using siRNA directed towards VEGF as an anti-angiogenic treatment.

Keywords: choroid: neovascularization • gene transfer/gene therapy • growth factors/growth factor receptors 
© 2003, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Permission to republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Office prior to publication.
Copyright © 2024 Association for Research in Vision and Ophthalmology.
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