Periocular injection of an adenoviral vector encoding pigment epithelium-derived factor inhibits choroidal neovascularization

P. Gehlbach, A. M. Demetriades, S. Yamamoto, T. Deering, E. J. Duh, H. S. Yang, C. Cingolani, H. Lai, L. Wei, P. A. Campochiaro

Research output: Contribution to journalArticlepeer-review

Abstract

Gene transfer provides an exciting new approach for the treatment of retinal and choroidal diseases. Two areas of concern are the potential for vector-related toxicity and uncertainties associated with prolonged transgene expression. One way to address these concerns for transfer of genes encoding secreted proteins is to transduce cells on the outside of the eye, provided the gene product can gain access to the eye and have the desired effect. In this study, we investigated the feasibility of this approach. Periocular injection of an adenoviral vector encoding β-galactosidase (AdLacZ.10) resulted in LacZ-stained cells throughout the orbit and around the eye. Compared to periocular injection of 5 × 109 particles of control vector, periocular injection of 5 × 109 or 1 × 109 particles of an adenoviral vector expressing pigment epithelium-derived factor (PEDF) regulated by a CMV promoter (AdPEDF.11) resulted in significantly elevated intraocular levels of PEDF and suppression of choroidal neovascularization. Periocularly injected recombinant PEDF was also found to diffuse through the sclera into the eye. Although similar experiments are needed in an animal with a human-sized eye, these data suggest that periocular gene transfer deserves consideration for the treatment of choroidal diseases.

Original languageEnglish (US)
Pages (from-to)637-646
Number of pages10
JournalGene Therapy
Volume10
Issue number8
DOIs
StatePublished - Apr 2003

Keywords

  • Adenoviral vectors
  • Age-related macular degeneration
  • Antingiogenesis
  • Choroidal diseases
  • Drug delivery
  • Neovascularization
  • PEDF

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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