Angiopoietin 1 inhibits ocular neovascularization and breakdown of the blood-retinal barrier

• Published in: Gene therapy Vol. 11; no. 10; pp. 865 - 873
• Main Authors: NAMBU, H, NAMBU, R, OSHIMA, Y, HACKETT, S. F, OKOYE, G, WIEGAND, S, YANCOPOULOS, G, ZACK, D. J, CAMPOCHIARO, P. A
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01-05-2004
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Angiopoietin; Angiopoietin-1 - genetics; Angiopoietin-1 - metabolism; Angiopoietin-1 - physiology; Animals; Applied cell therapy and gene therapy; Biological and medical sciences; Biotechnology; Blood vessels; Blood-Retinal Barrier - physiology; Cell differentiation, maturation, development, hematopoiesis; Cell physiology; Choroidal Neovascularization - etiology; Choroidal Neovascularization - metabolism; Choroidal Neovascularization - physiopathology; Diabetic retinopathy; Ectopic expression; Edema; Eye; Fundamental and applied biological sciences. Psychology; Gene expression; Gene therapy; Health. Pharmaceutical industry; Industrial applications and implications. Economical aspects; Ischemia; Ischemia - complications; Ischemia - metabolism; Medical sciences; Mice; Mice, Transgenic; Molecular and cellular biology; Permeability; Promoter Regions, Genetic; Retina; Retina - metabolism; Retinal Neovascularization - etiology; Retinal Neovascularization - metabolism; Retinal Neovascularization - physiopathology; Retinal Vessels - physiopathology; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transgenic mice; Vascular endothelial growth factor; Vascularization; Endocrinopathy; Edema; Retinopathy; choroidal neovascularization; Diabetes mellitus; Ang1; Retina; diabetic retinopathy; gene delivery; Angiogenesis; Macula; Eye disease; blood-retinal barrier; retinal neovascularization; macular edema; Neovascularization; Gene therapy; antiangiogenesis
• ISSN: 0969-7128; 1476-5462
• DOI: 10.1038/sj.gt.3302230

Several retinal and choroidal diseases are potentially treatable by intraocular delivery of genes whose products may counter or neutralize abnormal gene expression that occurs as part of the diseases. However, prior to considering a transgene, it is necessary to thoroughly investigate the effects of its expression in normal and diseased eyes. An efficient way to do this is to combine tissue-specific promoters with inducible promoter systems in transgenic mice. In this study, we used this approach to evaluate the effects of ectopic expression of angiopoietin-1 (Ang1) in normal eyes and those with ocular neovascularization. Adult mice with induced expression of Ang1 ubiquitously, or specifically in the retina, appeared normal and had no identifiable changes in retinal or choroidal blood vessels or in retinal function as assessed by electroretinography. Increased expression of Ang1 in eyes with severe retinal ischemia or in eyes with rupture of Bruch's membrane significantly suppressed the development of retinal or choroidal neovascularization, respectively. This inhibition of ocular neovascularization is particularly interesting and noteworthy, because overexpression of Ang1 in skin stimulates neovascularization. Ang1 also significantly reduced VEGF-induced retinal vascular permeability. These data suggest that intraocular delivery of ang1 has potential for treatment of ocular neovascularization and macular edema.