May 2003
Volume 44, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2003
Adeno-associated Delivery of TIMP-3 Inhibits Experimental Choroidal Neovascularization
Author Affiliations & Notes
  • K.C. Behling
    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
  • S.J. Reich
    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
  • M.J. Tolentino
    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
  • Footnotes
    Commercial Relationships  K.C. Behling, None; A. Kuroki, None; J. Fosnot, None; S.J. Reich, None; A.M. Maguire, None; M.J. Tolentino, None; J. Bennett, None.
  • Footnotes
    Support  NIH EY1341 and EY12156, RPB, IRRF, JDRF, FM Kirby Foundation
Investigative Ophthalmology & Visual Science May 2003, Vol.44, 1425. doi:
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      K.C. Behling, A. Kuroki, J. Fosnot, S.J. Reich, A.M. Maguire, M.J. Tolentino, J. Bennett; Adeno-associated Delivery of TIMP-3 Inhibits Experimental Choroidal Neovascularization . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1425.

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

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Abstract

Abstract: : Purpose: These experiments aim to determine if AAV2/1-mediated delivery of tissue inhibitor of metalloproteinase-3 (TIMP3) can inhibit experimental laser induced choroidal neovascularization (CNV) in mice. Methods: AAV2/1-CMV-TIMP3 was delivered unilaterally to adult female C57BL/6 mice via subretinal injections. Contralateral eyes received subretinal injections of AAV2/1-CMV-LacZ and served as controls. Three weeks post-injection, mice underwent laser photocoagulation using an 810 nm diode laser (OcuLight Six; IRIS Medical, Mountain View, CA). Three laser spots were applied in both eyes. Two weeks after laser treatment, animals were perfused with high molecular weight FITC-Dextran, and choroidal flat mounts were prepared and analyzed microscopically. The area of CNV was measured with Openlab software (Improvision, Boston, MA) in a masked fashion. Results: Flat mount analysis revealed a statistically significant decrease in CNV in AAV2/1-CMV-TIMP3-treated eyes when compared to controls. Conclusion: AAV2/1-CMV-TIMP3 can reduce neovascularization in a murine model of laser induced CNV and may be a promising method of inhibiting CNV in humans.

Keywords: choroid: neovascularization • gene transfer/gene therapy • animal model 
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