title: Lipid-mediated delivery of brain-specific angiogenesis inhibitor 1 gene reduces corneal neovascularization in an in vivo rabbit model.
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 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.
authors.affiliation: Department of Ophthalmology, Chonnam National University Medical School, Kwangju 501-190, South Korea.
authors.forename: K C
authors.initials: KC
authors.lastname: Yoon
authors.forename: K Y
authors.initials: KY
authors.lastname: Ahn
authors.forename: J H
authors.initials: JH
authors.lastname: Lee
authors.forename: B J
authors.initials: BJ
authors.lastname: Chun
authors.forename: S W
authors.initials: SW
authors.lastname: Park
authors.forename: M S
authors.initials: MS
authors.lastname: Seo
authors.forename: Y-G
authors.initials: YG
authors.lastname: Park
authors.forename: K K
authors.initials: KK
authors.lastname: Kim
mesh_terms: D042501:Angiogenic Proteins / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D003315:Cornea / Q000378:metabolism; D016510:Corneal Neovascularization / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage; D007167:Immunotherapy / Q000379:methods; D016023:Integrins / Q000276:immunology; D008055:Lipids; D011817:Rabbits; D043562:Receptors, G-Protein-Coupled; D019030:Receptors, Vitronectin / Q000276:immunology; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology / Q000378:metabolism
chemical_list: C468226:ADGRB1 protein, human; D042501:Angiogenic Proteins; D016023:Integrins; D008055:Lipids; D043562:Receptors, G-Protein-Coupled; D019030:Receptors, Vitronectin; D042461:Vascular Endothelial Growth Factor A; C064660:integrin alphaVbeta5