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

Gene Ther. 2005 Apr;12(7):617-24. doi: 10.1038/


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 alpha(v)beta(5) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenic Proteins / genetics*
  • Angiogenic Proteins / metabolism
  • Animals
  • Cornea / metabolism
  • Corneal Neovascularization / metabolism
  • Corneal Neovascularization / pathology
  • Corneal Neovascularization / therapy*
  • Disease Models, Animal
  • Gene Transfer Techniques*
  • Genes, Reporter
  • Genetic Therapy / methods*
  • Genetic Vectors / administration & dosage
  • Immunotherapy / methods
  • Integrins / immunology
  • Lipids
  • Rabbits
  • Receptors, G-Protein-Coupled
  • Receptors, Vitronectin / immunology
  • Vascular Endothelial Growth Factor A / immunology
  • Vascular Endothelial Growth Factor A / metabolism


  • ADGRB1 protein, human
  • Angiogenic Proteins
  • Integrins
  • Lipids
  • Receptors, G-Protein-Coupled
  • Receptors, Vitronectin
  • Vascular Endothelial Growth Factor A
  • integrin alphaVbeta5