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- Title
Long-term Evaluation of AAV-Mediated sFlt-1 Gene Therapy for Ocular Neovascularization in Mice and Monkeys
- Authors
Lai, Chooi-May; Shen, Wei-Yong; Brankov, Meliha; Lai, Yvonne K.Y.; Barnett, Nigel L.; Lee, Shu-Yen; Yeo, Ian Y.S.; Mathur, Ranjana; Ho, Joseph E.S.; Pineda, Paul; Barathi, Amutha; Ang, Chong-Lye; Constable, Ian J.; Rakoczy, Elizabeth P.
- Abstract
Abstract: Vascular endothelial growth factor (VEGF) is one of the major mediators of retinal ischemia-associated neovascularization. We have shown here that adeno-associated virus (AAV)-mediated expression of sFlt-1, a soluble form of the Flt-1 VEGF receptor, was maintained for up to 8 and 17 months postinjection in mice and in monkeys, respectively. The expression of sFlt-1 was associated with the long-term (8 months) regression of neovascular vessels in 85% of trVEGF029 eyes. In addition, it resulted in the maintenance of retinal morphology, as the majority of the treated trVEGF029 eyes (75%) retained high numbers of photoreceptors, and in retinal function as measured by electroretinography. AAV-mediated expression of sFlt-1 prevented the development of laser photocoagulation-induced choroidal neovascularization in all treated monkey eyes. There were no clinically or histologically detectable signs of toxicity present in either animal model following AAV.sFlt injection. These results suggest that AAV-mediated secretion gene therapy could be considered for treatment of retinal and choroidal neovascularizations.
- Subjects
NEOVASCULARIZATION; GENETIC engineering; GENETIC recombination; ANIMAL culture
- Publication
Molecular Therapy, 2005, Vol 12, Issue 4, p659
- ISSN
1525-0016
- Publication type
Article
- DOI
10.1016/j.ymthe.2005.04.022