1. ¹Department of Ophthalmology, Chonnam National University Medical School, Kwangju, South Korea
2. ²Medical Research Center for Gene Regulation and the Brain Korea 21 Project, Center for Biomedical Human Resources at Chonnam National University, Chonnam National University Medical School, Kwangju, South Korea

Correspondence: Professor KK Kim, Department of Pharmacology, Chonnam National University Medical School, Hak-Dong 5, Dong-Ku, Kwangju 501-190, South Korea. E-mail: kimkk@chonnam.ac.kr

Received 26 January 2008; Revised 31 January 2009; Accepted 10 February 2009; Published online 7 May 2009.

Abstract

Corneal neovascularization can reduce visual acuity. GA-binding protein (GABP) is a transcription factor that regulates the expression of target genes including vascular endothelial growth factor (VEGF) and roundabout4 (Robo4), which participate in pathologic angiogenesis. We assessed whether intraocular injection of the GABP gene affects the growth of new corneal blood vessels in a mouse ocular neovascularization model. Transfection of human GABP and GABP gene (GABP/) into human conjunctival epithelial cells resulted in decreased VEGF and Robo4 expression. Three groups of mice underwent chemical and mechanical denudation of the corneal epithelium. Subsequently, two groups were administered subconjunctival injection of lipoplexes carrying plasmid DNA encoding for human GABP/ or an empty plasmid DNA at 1-week intervals. The third group served as an experimental control. In vivo delivery of human GABP/ into mouse neovascularized cornea reduced VEGF and Robo4 gene expression. Biomicroscopic examination showed that, at 1 week after one or two injections, GABP/-treated eyes had significantly less neovascularized corneal area than did eyes treated with the empty vector. Histologic examination showed significantly less vascularized area and fewer blood vessels in the GABP-treated group at 1 week after injections. However, these angiosuppressive effects were weakened at 2 weeks after injections. Our results indicate that subconjunctival GABP gene delivery delays corneal neovascularization for up to 2 weeks in a mouse model of deliberate corneal injury.