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

H. Nambu, R. Nambu, Y. Oshima, S. F. Hackett, G. Okoye, S. Wiegand, G. Yancopoulos, D. J. Zack, P. A. Campochiaro

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)865-873
Number of pages9
JournalGene Therapy
Volume11
Issue number10
DOIs
StatePublished - May 1 2004

Keywords

  • Ang1
  • Antiangiogenesis
  • Blood-retinal barrier
  • Choroidal neovascularization
  • Diabetic retinopathy
  • Gene delivery
  • Macular edema
  • Retinal neovascularization

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Fingerprint Dive into the research topics of 'Angiopoietin 1 inhibits ocular neovascularization and breakdown of the blood-retinal barrier'. Together they form a unique fingerprint.

  • Cite this

    Nambu, H., Nambu, R., Oshima, Y., Hackett, S. F., Okoye, G., Wiegand, S., Yancopoulos, G., Zack, D. J., & Campochiaro, P. A. (2004). Angiopoietin 1 inhibits ocular neovascularization and breakdown of the blood-retinal barrier. Gene Therapy, 11(10), 865-873. https://doi.org/10.1038/sj.gt.3302230