May 2005
Volume 46, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2005
AAV2–Mediated Expression of Anti–Angiogenic Factors Inhibits Sub–Retinal Neovascularization in the VLDLR –/– Mouse
Author Affiliations & Notes
  • J.G. Flannery
    School of Optometry and Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, CA
  • J. Lee
    School of Optometry and Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, CA
  • N. Walsh
    School of Optometry and Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, CA
  • I.R. Zolfaghar
    School of Optometry and Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, CA
  • V. Chiodo
    Department of Ophthalmology, University of Florida, Gainesville, FL
  • C. Xia
    School of Optometry, University of California Berkeley, Berkeley, CA
  • X. Gong
    School of Optometry, University of California Berkeley, Berkeley, CA
  • W.W. Hauswirth
    Department of Ophthalmology, University of Florida, Gainesville, FL
  • Footnotes
    Commercial Relationships  J.G. Flannery, None; J. Lee, None; N. Walsh, None; I.R. Zolfaghar, None; V. Chiodo, None; C. Xia, None; X. Gong, None; W.W. Hauswirth, AGTC P.
  • Footnotes
    Support  NEI/NIH EY013533 and The Foundation Fighting Blindness
Investigative Ophthalmology & Visual Science May 2005, Vol.46, 5253. doi:
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      J.G. Flannery, J. Lee, N. Walsh, I.R. Zolfaghar, V. Chiodo, C. Xia, X. Gong, W.W. Hauswirth; AAV2–Mediated Expression of Anti–Angiogenic Factors Inhibits Sub–Retinal Neovascularization in the VLDLR –/– Mouse . Invest. Ophthalmol. Vis. Sci. 2005;46(13):5253.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Abstract: : Purpose: We tested whether AAV–2 mediated delivery of PEDF, K1K3, Endostatin or the inhibitory domains of VEGF (exons 6 and 7), can decrease the growth and permeability of abnormal vessels in the VLDLR –/– mouse. Methods: To establish a pre–treatment baseline, fundus imaging and fluorescein angiography were performed at age P28, in both right and left eyes. The following day, 2ul of AAV2 vectors containing either PEDF, Endostatin, K1K3, exon–6 or exon–7 derived VEGF peptides were delivered via intravitreal injection to the right eye. Left eyes were treated with a PBS sham injection. Animals were followed up to age P180 and the effect of overexpression of the anti–angiogenic agents was determined by analysis of fluorescein angiography at 3, 6 and 10 weeks post– injection. Three–dimensional reconstructions of retinal flat mounts were performed following perfusion of animals with a lipophilic vessel dye, and quantitative measurements of vessel length and volume were computed from these reconstructions. Results: To control for the variable number of leaky foci between eyes, changes in vessel permeability with age, were represented as a ratio of the number of foci found at baseline (i.e. P27–29). Preliminary data suggest that each of the anti–angiogenic factors significantly reduces the number of leaky foci when compared to PBS treated control eyes. Conclusions:These five anti–angiogenic molecules when delivered via AAV significantly reduced retinal neovascularization in the VLDLR mutant mouse model. This gene delivery approach may prove useful for the treatment of other causes of retinal neovascularization in diabetic retinopathy and the wet from of age–related macular degeneration.

Keywords: retinal neovascularization • gene transfer/gene therapy • transgenics/knock-outs 
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