Abstract |
The purpose of this study was to evaluate the efficacy of gene delivery of angiogenesis inhibitor, vasostatin (VS), in suppressing experimental model of choroidal neovascularization (CNV). A mammalian expression vector carrying VS, pCMV3-VS, was constructed and evaluated for its ability to produce VS in transfected cells using western blot analysis and a cell viability assay. CNV was induced in Brown Norway rats by fundus argon laser photocoagulation and evaluated by fundus fluorescein angiography (FAG). Ten days post- laser treatment, gene delivery was achieved by intramuscular (IM) injection of poly-( N-vinyl pyrrolidone) ( PVP) polymer conjugated with pCMV3-VS (PVP-VS) or a control vector (PVP-vector). Systemic VS expression was analysed by western blot analysis and enzyme linked immunosorbent assay (ELISA), and the extent of CNV was monitored by FAG analysis at different time intervals post-PVP treatment. Transfection of pCMV3-VS into muscle cells resulted in increased production and release of exogenous VS, which specifically inhibited the proliferation of endothelial cells. Besides, IM injection of PVP-VS, but not PVP-vector, led to elevated VS level in plasma for 30 days. After laser photocoagulation, rats injected with PVP-VS exhibited significantly lower incidence of CNV comparing with animals of control groups (P < 0.01) for at least 42 days. Moreover, rats treated with PVP-VS also showed a significant reduction in the CNV lesions compared with control groups (P < 0.001) for at least 42 days. Above all, no overt adverse effects were observed in rats received PVP-VS. These results demonstrate the potential of IM VS gene delivery for CNV treatment.
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Authors | Shwu-Jiuan Sheu, Li-Chen Chou, Youn-Shen Bee, Jane-Fane Chen, Hsiu-Chen Lin, Pey-Ru Lin, Hsing-Chun Lam, Ming-Hong Tai |
Journal | Experimental eye research
(Exp Eye Res)
Vol. 81
Issue 6
Pg. 673-9
(Dec 2005)
ISSN: 0014-4835 [Print] England |
PMID | 15967435
(Publication Type: Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Angiogenesis Inhibitors
- Calreticulin
- Peptide Fragments
- vasostatin
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Topics |
- Angiogenesis Inhibitors
(blood, genetics, metabolism)
- Animals
- Calreticulin
(blood, genetics, metabolism)
- Choroidal Neovascularization
(etiology, prevention & control)
- Enzyme-Linked Immunosorbent Assay
(methods)
- Feasibility Studies
- Gene Expression
- Genetic Therapy
(methods)
- Genetic Vectors
- Injections, Intramuscular
- Light Coagulation
- Peptide Fragments
(blood, genetics, metabolism)
- Rats
- Rats, Inbred BN
- Transfection
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