Lipid-mediated delivery of brain-specific angiogenesis inhibitor 1 gene reduces corneal neovascularization in an in vivo rabbit model
| Autor: | Sang Woo Park, Kyung Keun Kim, Yeoung Geol Park, Kyuyoun Ahn, Ji Hee Lee, Kyung Chul Yoon, Byeong Jo Chun, Man-Seong Seo |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Vascular Endothelial Growth Factor A
Integrins medicine.medical_specialty genetic structures Angiogenesis Genetic Vectors Gene delivery Biology Receptors G-Protein-Coupled Cornea Neovascularization Genes Reporter In vivo Ophthalmology Genetics medicine Animals Corneal Neovascularization Receptors Vitronectin Angiogenic Proteins Molecular Biology Gene Transfer Techniques Genetic Therapy medicine.disease Lipids eye diseases Surgery Angiogenesis inhibitor Disease Models Animal Vascular endothelial growth factor A medicine.anatomical_structure Corneal neovascularization Molecular Medicine Immunotherapy Rabbits sense organs medicine.symptom hormones hormone substitutes and hormone antagonists |
| Zdroj: | Gene Therapy. 12:617-624 |
| ISSN: | 1476-5462 0969-7128 |
| DOI: | 10.1038/sj.gt.3302442 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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