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Hum Gene Ther. 2005 Apr;16(4):473-8.

Periocular gene transfer of pigment epithelium-derived factor inhibits choroidal neovascularization in a human-sized eye.

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1
The Department of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.

Abstract

Gene transfer provides a potential way to achieve sustained delivery of therapeutic proteins to the eye. Studies in rodents have suggested that periocular injection of adenoviral vectors containing expression cassettes for antiangiogenic proteins results in high intraocular levels of the proteins and suppression of choroidal neovascularization (CNV). However, the differences in size and scleral thickness between mouse and human eyes make it difficult to ascertain if periocular gene transfer is a feasible approach for treating human choroidal diseases. To address this issue, we tested the effect of periocular injection of an expression cassette for pigment epithelium-derived factor (PEDF) packaged in adenoviral vector (AdPEDF.11) in a CNV model in pigs, which have eyes that are very similar to humans in size and scleral thickness. Periocular injection of beta-galactosidase (AdLacZ.11) resulted in prominent transduction of periocular tissues, as was seen in mice. Periocular injection of AdPEDF.11 caused increased levels of PEDF in the choroid and significantly reduced the amount of CNV at rupture sites in Bruch's membrane. These data suggest that periocular gene transfer may be feasible for treatment of human choroidal diseases.

PMID:
15871678
DOI:
10.1089/hum.2005.16.473
[Indexed for MEDLINE]
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