May 2003
Volume 44, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2003
Duration of Antiangiogenic Effect Following Periocular Delivery of Ad.PEDF.11 in Mice with Laser-Induced Choroidal Neovascularization (CNV)
Author Affiliations & Notes
  • P.L. Gehlbach
    Ophthalmology, Wilmer Eye Inst-JHU, Baltimore, MD, United States
  • T. Deering
    Ophthalmology, Wilmer Eye Inst-JHU, Baltimore, MD, United States
  • S. Yamamoto
    Ophthalmology, Wilmer Eye Inst-JHU, Baltimore, MD, United States
  • Y. Oshima
    Ophthalmology, Wilmer Eye Inst-JHU, Baltimore, MD, United States
  • H. Nambu
    Ophthalmology, Wilmer Eye Inst-JHU, Baltimore, MD, United States
  • K. Callahan
    Ophthalmology, Wilmer Eye Inst-JHU, Baltimore, MD, United States
  • L. Wei
    Ophthalmology, Wilmer Eye Inst-JHU, Baltimore, MD, United States
  • P.A. Campochiaro
    Ophthalmology, Wilmer Eye Inst-JHU, Baltimore, MD, United States
  • Footnotes
    Commercial Relationships  P.L. Gehlbach, GenVec, Inc F; T. Deering, None; S. Yamamoto, None; Y. Oshima, None; H. Nambu, None; K. Callahan, None; L. Wei, GenVec, Inc. E; P.A. Campochiaro, Novartis Ophthalmic F, C, R; GenVec, Inc. F.
  • Footnotes
    Support  NIH Grant EYO5951, EY12609, KO8EY13420, JDRFI
Investigative Ophthalmology & Visual Science May 2003, Vol.44, 3578. doi:
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      P.L. Gehlbach, T. Deering, S. Yamamoto, Y. Oshima, H. Nambu, K. Callahan, L. Wei, P.A. Campochiaro; Duration of Antiangiogenic Effect Following Periocular Delivery of Ad.PEDF.11 in Mice with Laser-Induced Choroidal Neovascularization (CNV) . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3578.

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

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Abstract

Abstract: : Purpose: Intraocular or periocular injection of E1-, E3-, E4- deleted adenoviral vector encoding human pigment epithelium-derived factor (Ad.PEDF.11) at the time of laser-induced rupture of Bruch’s membrane, suppresses the development of CNV. The aim of this study was to determine the duration of antiangiogenic effect after periocular injection of Ad.PEDF.11. Methods: Thirty-six C57Bl6 mice received periocular injection of 5x109 particles of AdPEDF.11 in the right eye and no injection in the left eye. At weeks 1, 2 and 4 following vector injection Bruch’s membrane was ruptured with laser in 3 locations. Two weeks after laser treatment, mice were perfused with fluorescein- labeled dextran, choroidal flat mounts were dissected, and the area of CNV was measured at Bruch’s membrane rupture sites. CNV area was compared between treated and control eyes at each time point using a paired t-test assuming equal variance with alpha assigned a value of 0.05. Results: Eyes treated with laser, 1 week or 2 weeks after periocular injection of Ad.PEDF.11, showed significantly smaller areas of CNV at Bruch’s membrane rupture sites compared to untreated fellow eyes. At 1 week: (0.021 mm2 vs. 0.032 mm2, p=0.028), at 2 weeks: (0.02 mm2 vs. 0.031 mm2, p=0.017). When Bruch’s membrane was ruptured 4 weeks after injection of Ad.PEDF.11, there was no significant difference between treated and untreated eyes: (0.032 mm2 vs. 0.047 mm2, p=0.27). Conclusions: These data indicate that the antiangiogenic effect conferred by periocular injection of 5x109 particles of Ad.PEDF.11 is sufficient between 2 and 4 weeks after injection to significantly suppress development of CNV.

Keywords: gene transfer/gene therapy • adenovirus • choroid: neovascularization 
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