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Lipid-mediated delivery of brain-specific angiogenesis inhibitor 1 gene reduces corneal neovascularization in an in vivo rabbit model

Gene Therapy volume 12, pages 617–624 (2005)Cite this article

Abstract

Corneal neovascularization, which occurs in many pathologic states of the cornea, reduces the visual acuity. Recently, we found that the extracellular region of brain-specific angiogenesis inhibitor 1 (BAI1-ECR) has antiproliferative activity through functional blocking of αvβ5 integrin in endothelial cells. In this study, we investigated the effects of lipid-mediated subconjunctival injection of the BAI1-ECR gene on corneal angiogenesis induced by epithelial debridement by heptanol in the rabbit. When a pEGFP-BAI1-ECR plasmid was given subconjunctivally 1 week after epithelial debridement, green fluorescence was detected in the corneal stroma with expression persisting for 7 days. To test the effect of BAI1-ECR on neovascularization, rabbits were injected with the BAI1-ECR gene or empty vector two or three times at 1-week intervals beginning 1 week after debridement. When measured with biomicroscopy at 1 or 2 weeks after two weekly injections, BAI1-delivered eyes had significantly less neovascularized corneal area than vector-injected ones in both time periods. Similar microscopic results were obtained after three weekly injections of BAI1-ECR. In quantitative histological examination, the BAI1-receiving eyes showed significantly less neovascular area and number of vessels than vector-injected ones. Also, after two weekly injections, BAI1-delivered eyes had decreased neovascularized corneal area equivalent to that of anti-VEGF antibody-injected ones. These results indicate that BAI1-ECR gene delivery effectively reduces experimental corneal neovascularization and suggest that the BAI1-ECR protein can be used as an angiogenesis suppressor in the eye.

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Acknowledgements

We thank Song Eun Lee for assisance with immunohistochemistry and Jennifer Macke for assistance in preparing the text. This work was supported by the Korea Science & Engineering Foundation through the Medical Research Center for Gene Regulation (R13-2002-013-02000-0) at Chonnam National University.

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Authors and Affiliations

  1. Department of Ophthalmology, Chonnam National University Medical School, Kwangju, South Korea

    K C Yoon, S W Park, M S Seo & Y-G Park

  2. Medical Research Center for Gene Regulation, Chonnam National University Medical School, Kwangju, South Korea

    K Y Ahn, J H Lee, B J Chun & K K Kim

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  1. K C Yoon
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Yoon, K., Ahn, K., Lee, J. et al. Lipid-mediated delivery of brain-specific angiogenesis inhibitor 1 gene reduces corneal neovascularization in an in vivo rabbit model. Gene Ther 12, 617–624 (2005). https://doi.org/10.1038/sj.gt.3302442

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