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

Authors :
Elia J. Duh
T. Deering
C Cingolani
S Yamamoto
H Lai
Anna M. Demetriades
Hoseong S. Yang
Peter A. Campochiaro
Peter L. Gehlbach
L.L. Wei
Source :
Gene Therapy. 10:637-646
Publication Year :
2003
Publisher :
Springer Science and Business Media LLC, 2003.

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 beta-galactosidase (AdLacZ.10) resulted in LacZ-stained cells throughout the orbit and around the eye. Compared to periocular injection of 5 x 10(9) particles of control vector, periocular injection of 5 x 10(9) or 1 x 10(9) 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.

Details

ISSN :
14765462 and 09697128
Volume :
10
Database :
OpenAIRE
Journal :
Gene Therapy
Accession number :
edsair.doi.dedup.....26df179cbc18628d69311f6b29bf36a8