title: Angiopoietin 1 inhibits ocular neovascularization and breakdown of the blood-retinal barrier.
abstract: 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.
authors.affiliation: The Department of Ophthalmology, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Maumenee 719, Baltimore, MD, USA.
authors.forename: H
authors.initials: H
authors.lastname: Nambu
authors.forename: R
authors.initials: R
authors.lastname: Nambu
authors.forename: Y
authors.initials: Y
authors.lastname: Oshima
authors.forename: S F
authors.initials: SF
authors.lastname: Hackett
authors.forename: G
authors.initials: G
authors.lastname: Okoye
authors.forename: S
authors.initials: S
authors.lastname: Wiegand
authors.forename: G
authors.initials: G
authors.lastname: Yancopoulos
authors.forename: D J
authors.initials: DJ
authors.lastname: Zack
authors.forename: P A
authors.initials: PA
authors.lastname: Campochiaro
mesh_terms: D042683:Angiopoietin-1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001813:Blood-Retinal Barrier / Q000502:physiology*; D020256:Choroidal Neovascularization / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D007511:Ischemia / Q000150:complications / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D012160:Retina / Q000378:metabolism; D015861:Retinal Neovascularization / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D012171:Retinal Vessels / Q000503:physiopathology
chemical_list: D042683:Angiopoietin-1