May 2006
Volume 47, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2006
Longevity and Toxicity of AAV–Mediated sFLT–1 Gene Therapy for Ocular Neovascularization in Mice and Monkeys
E.P. Rakoczy; C.–M. Lai; W.–Y. Shen; M. Brankov; N. Barnett; S.–Y. Lee; I. Yeo; C.–L. Ang; M. Degli–Esposti; S. Dunlop
Author Affiliations & Notes
  • E.P. Rakoczy
    The University of Western Australia, Perth, Australia
    Centre for Ophthalmology and Visual Science,
  • C.–M. Lai
    The University of Western Australia, Perth, Australia
    Centre for Ophthalmology and Visual Science,
  • W.–Y. Shen
    The University of Western Australia, Perth, Australia
    Centre for Ophthalmology and Visual Science,
    Molecular Ophthalmology Department, Lions Eye Institute, Nedlands, Australia
  • M. Brankov
    The University of Western Australia, Perth, Australia
    Centre for Ophthalmology and Visual Science,
    Molecular Ophthalmology Department, Lions Eye Institute, Nedlands, Australia
  • N. Barnett
    Molecular Ophthalmology Department, Lions Eye Institute, Nedlands, Australia
    Vision, Touch & Hearing Research Centre, The University of Queensland, Queensland, Australia
  • S.–Y. Lee
    Singapore National Eye Centre, Singapore, Singapore
  • I. Yeo
    Singapore National Eye Centre, Singapore, Singapore
  • C.–L. Ang
    Singapore National Eye Centre, Singapore, Singapore
  • M. Degli–Esposti
    The University of Western Australia, Perth, Australia
    Centre for Experimental Immunology,
  • S. Dunlop
    The University of Western Australia, Perth, Australia
    School of Animal Biology,
  • Footnotes
    Commercial Relationships  E.P. Rakoczy, None; C. Lai, None; W. Shen, None; M. Brankov, None; N. Barnett, None; S. Lee, None; I. Yeo, None; C. Ang, None; M. Degli–Esposti, None; S. Dunlop, None.
  • Footnotes
    Support  NHMRC, JDRF
Investigative Ophthalmology & Visual Science May 2006, Vol.47, 833. doi:
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      E.P. Rakoczy, C.–M. Lai, W.–Y. Shen, M. Brankov, N. Barnett, S.–Y. Lee, I. Yeo, C.–L. Ang, M. Degli–Esposti, S. Dunlop; Longevity and Toxicity of AAV–Mediated sFLT–1 Gene Therapy for Ocular Neovascularization in Mice and Monkeys . Invest. Ophthalmol. Vis. Sci. 2006;47(13):833.

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Abstract

Purpose: : To investigate the efficacy, longevity and toxicity of adeno–associated virus (AAV)–mediated expression of sFlt–1 in the mouse model of retinal neovascularization (trVEGF029) and in the laser induced monkey model of choroidal neovascularization.

Methods: : rAAV.sFLT was injected subretinally into trVEGF029 mouse (26) and laser induced monkey (4) eyes. Fluorescence Angiography, histology and immunologycal techniques were used to measure the efficacy, longevity and toxicity of the viral construct.

Results: : Transgene expression were to maintained up to 8 and 17 months post–injection in mice and monkeys, respectively. The expression of sFlt–1 was associated with the long–term (8 months) regression of neovascular vessels in 85% of trVEGF029 eyes. The majority of the treated trVEGF029 eyes (75%) retained high numbers of photoreceptors. AAV–mediated expression of sFlt–1 prevented the development of laser photocoagulation–induced choroidal neovascularization in all treated monkey eyes. There were no clinically or histologically detectable signs of toxicity present in either models following AAV.sFlt injection.

Conclusions: : These results suggest that AAV–mediated secretion gene therapy could be considered for treatment of retinal and choroidal neovascularization in chronic diseases.

Keywords: age-related macular degeneration • diabetic retinopathy • gene transfer/gene therapy 
© 2006, 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 © 2025 Association for Research in Vision and Ophthalmology.
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