May 2004
Volume 45, Issue 13
ARVO Annual Meeting Abstract  |   May 2004
Intraocular Gene Delivery of Soluble VEGF Receptors
Author Affiliations & Notes
  • P. Pechan
    Gene Therapy, Genzyme Corporation, Framingham, MA
  • M. Lukason
    Gene Therapy, Genzyme Corporation, Framingham, MA
  • H.L. Rubin
    Gene Therapy, Genzyme Corporation, Framingham, MA
  • A. Scaria
    Gene Therapy, Genzyme Corporation, Framingham, MA
  • S. Wadsworth
    Gene Therapy, Genzyme Corporation, Framingham, MA
  • Footnotes
    Commercial Relationships  P. Pechan, Genzyme Corp. E; M. Lukason, Genzyme Corp. E; H.L. Rubin, Genzyme Corp. E; A. Scaria, Genzyme Corp. E; S. Wadsworth, Genzyme Corp. E.
  • Footnotes
    Support  none
Investigative Ophthalmology & Visual Science May 2004, Vol.45, 3712. doi:
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    • Get Citation

      P. Pechan, M. Lukason, H.L. Rubin, A. Scaria, S. Wadsworth; Intraocular Gene Delivery of Soluble VEGF Receptors . Invest. Ophthalmol. Vis. Sci. 2004;45(13):3712.

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

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Abstract: : Purpose:Many studies have shown that vascular endothelial growth factor (VEGF) plays a critical role in development of choroidal and retinal neovascularization. Therefore, antagonizing VEGF is a potentially useful strategy for treating such disorders. In current study we are evaluating the relative efficacy of various truncated and full–length versions of soluble VEGF receptors, VEGF–R1 (sFlt–1) and VEGF–R2 (sKDR), toward inhibiting neovascularization. Methods:Biological potency of various versions was ranked in vitro using Human Vascular Endothelial Cell (HUVEC) proliferation and migration assays. Candidate genes were then inserted into adenovirus type 2 (Ad2) or adeno–associated virus type 2 (AAV2) gene transfer vectors. The efficacy of Ad2 and AAV2 vectors is being evaluated in vivo by intravitreal injection in the mouse retinopathy of prematurity (ROP) model. The extent of retinal neovascularization is measured both by fluorescein angiography and histology. Results:Several versions of sFlt–1 were potent inhibitors of VEGF–dependent HUVEC proliferation and migration assays. Our preliminary results show that intravitreal delivery of 5x108 particles of Ad2/sFlt–1 significantly decreased retinal neovascularization in the ROP model. Evaluation of safety and efficacy following single and multiple vector administrations is underway. Conclusions:As reported by other investigators, intravitreal injection is an efficient method of gene transfer into the eye. Virus vector mediated delivery of sFlt–1 appears to be a promising tool for the inhibition of retinal neovascularization.

Keywords: gene transfer/gene therapy • retinal neovascularization • growth factors/growth factor receptors 

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