May 2004
Volume 45, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2004
Periocular Injection of Adenoviral Vectors Expressing Pigment Epithelium–Derived Factor (PEDF) Suppresses Choroidal Neovascularization (CNV) in Pigs
Y. Saishin; R. Lima Silva; Y. Saishin; H. Lai; M. Carrion; B. Harris; M. Hamilton; L. Wei; P.A. Campochiaro
Author Affiliations & Notes
  • Y. Saishin
    The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD
  • R. Lima Silva
    The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD
  • Y. Saishin
    The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD
  • H. Lai
    The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD
  • M. Carrion
    Gen Vec, Inc., Gaithersburg, MD
  • B. Harris
    Gen Vec, Inc., Gaithersburg, MD
  • M. Hamilton
    Gen Vec, Inc., Gaithersburg, MD
  • L. Wei
    Gen Vec, Inc., Gaithersburg, MD
  • P.A. Campochiaro
    The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD
  • Footnotes
    Commercial Relationships  Y. Saishin, None; R. Lima Silva, None; Y. Saishin, None; H. Lai, None; M. Carrion, Gen Vec, Inc. E; B. Harris, Gen Vec, Inc. E; M. Hamilton, Gen Vec, Inc. E; L. Wei, Gen Vec, Inc. E; P.A. Campochiaro, None.
  • Footnotes
    Support  none
Investigative Ophthalmology & Visual Science May 2004, Vol.45, 1848. doi:
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      Y. Saishin, R. Lima Silva, Y. Saishin, H. Lai, M. Carrion, B. Harris, M. Hamilton, L. Wei, P.A. Campochiaro; Periocular Injection of Adenoviral Vectors Expressing Pigment Epithelium–Derived Factor (PEDF) Suppresses Choroidal Neovascularization (CNV) in Pigs . Invest. Ophthalmol. Vis. Sci. 2004;45(13):1848.

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Abstract

Abstract: : Purpose: Intraocular or periocular injection of adenoviral vectors containing an expression construct for PEDF (AdPEDF.11) suppresses CNV in mice. This study sought to determine if periocular injection of AdPEDF.11 could suppress CNV in the human–sized eyes of pigs. Methods: Four week–old female Yorkshire pigs had laser–induced rupture of Bruch’s membrane at 8 locations in each eye followed by periocular injection of 0.5 or 1.0 ml of 1012 pu/ml of AdPEDF.11 or AdNull.11 in one eye and periocular injection of 0.5 or 1.0 ml of vehicle in the fellow eye. After 10 days, the pigs were euthanized and the area of CNV was quantitated by image analysis of serial sections cut through each CNV lesion. For expression studies, one pig had periocular injection of 1 ml containing 1012 pu/ml of AdPEDF.11 in one eye and periocular injection of 1012 pu/ml of AdLacZ.11 in the fellow eye. After 3 days the pig was euthanized and orbital sections were stained for LacZ for the eye injected with AdLacZ.11, and for the eye injected with AdPEDF.11, the vitreous, retina, choroid, sclera, and periocular tissue were dissected and homogenized, and PEDF levels were measured by ELISA. Results: Three days after periocular injection of 1.0 ml of 1012 pu/ml of AdLacZ.11, there was widespread staining for LacZ surrounding the entire globe. Three days after periocular injection of 1.0 ml of 1012 pu/ml of AdPEDF.11, levels of PEDF in pg/µg total protein were 109.8 in periocular tissue, 105.2 in sclera, 6.5 in choroid, 9.2 in vitreous, and undetectable in retina. Periocular injection of 0.5 (0.18 ± 0.009) or 1.0 ml (0.15 ± 0.01) of 1012 pu/ml of AdPEDF.11 resulted in significantly less CNV per rupture site than periocular injection of 0.5 (0.22 ± 0.009) or 1.0 ml (0.22 ± 0.01) of 1012 pu/ml of AdNull.11 or 0.5 (0.21 ± 0.006) or 1.0 ml (0.21 ± 0.007) of vehicle. Conclusions: Periocular injection of AdPEDF.11 results in strong transduction of periocular tissue resulting in detectable levels of PEDF in the eye and significant inhibition of CNV. These results in a human–sized eye suggest that periocular gene transfer may be feasible for treatment of ocular diseases.

Keywords: choroid: neovascularization • drug toxicity/drug effects • neovascularization 
© 2004, 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 © 2024 Association for Research in Vision and Ophthalmology.
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