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Inhibition of corneal neovascularization with endostatin delivered by adeno-associated viral (AAV) vector in a mouse corneal injury model

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Journal of Biomedical Science

Abstract

The use of a recombinant adeno-associated viral (rAAV) vector carrying endostatin gene as an anti-angiogenesis strategy to treat corneal neovascularization in a mouse model was evaluated. Subconjunctival injection of recombinant endostatin-AAV was used to examine the inhibition of corneal neovascularization induced by silver nitrate cauterization in mice. The results showed that gene expression in corneal tissue was observed as early as 4 days after gene transfer and stably lasted for over 8 months with minimal immune reaction. Subconjunctival injection of a high-titer rAAV-endostatin successfully inhibited neovascularization. Immunohistchemistry staining of CD 31 and endostatin showed that the treatment significantly inhibits angiogenesis in cornea. We concluded that the rAAV was capable of directly delivering genes to the ocular surface epithelium by way of subconjunctival injection and was able to deliver sustained, high levels of gene expression in vivo to inhibit angiogenesis.

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Acknowledgements

The authors acknowledge Dr. Shi-Yuan Cheng for kindly providing endostatin antibody for Immunohistochemistry stain. The authors thank Jian Zhang for the expert technical assistance. The authors thank Nicole for reviewing the paper. This work was supported in part by NIH grants 93-2314-B-182A-041.

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Authors and Affiliations

  1. Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Kwei San, Tao Yuan, 333, Taiwan

    Li-Ju Lai & June H. Wu

  2. Department of Ophthalmology, Chang Gung Memorial Hospital, 199 Tung-Hwa North Road, Taipei, 105, Taiwan

    Li-Ju Lai

  3. Department of Molecular Genetics and Biochemistry, University of Pittsburgh, Pittsburgh, PA, 15213, USA

    Li-Ju Lai & Xiao Xiao

  4. Department of Microbiology and Immunology, College of Medicine, Chang Gung University, Kwei San, Tao Yuan, 333, Taiwan

    June H. Wu

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  1. Li-Ju Lai
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  2. Xiao Xiao
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  3. June H. Wu
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Correspondence to June H. Wu.

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Lai, LJ., Xiao, X. & Wu, J.H. Inhibition of corneal neovascularization with endostatin delivered by adeno-associated viral (AAV) vector in a mouse corneal injury model. J Biomed Sci 14, 313–322 (2007). https://doi.org/10.1007/s11373-007-9153-7

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  • DOI: https://doi.org/10.1007/s11373-007-9153-7

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