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Encapsulated Cell Technology for the Delivery of Biologics to the Mouse Eye
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Encapsulated Cell Technology for the Delivery of Biologics to the Mouse Eye

Published on: March 30, 2020

Angiogenesis inhibition and choroidal neovascularization suppression by sustained delivery of an integrin antagonist,

Yingli Fu1, M Lourdes Ponce, Michelle Thill

  • 1National Eye Institute, NIH, Bethesda, MD, USA.

Investigative Ophthalmology & Visual Science
|October 27, 2007
PubMed
Abstract

Insights

Sustained delivery of EMD478761, an alpha(v)beta(3)/alpha(v)beta(5) integrin antagonist, effectively inhibited angiogenesis in chick embryos and suppressed choroidal neovascularization in rats. This suggests potential for treating neovascular eye diseases.

Area of Science:

  • Ophthalmology
  • Angiogenesis Research
  • Drug Delivery Systems

Background:

  • Neovascular ocular diseases are a leading cause of vision loss.
  • Targeting angiogenesis, the formation of new blood vessels, is a key therapeutic strategy.
  • Alpha(v)beta(3)/alpha(v)beta(5) integrins play a crucial role in angiogenesis.

Purpose of the Study:

  • To evaluate the antiangiogenic effects of EMD478761, an alpha(v)beta(3)/alpha(v)beta(5) integrin antagonist.
  • To assess sustained release of EMD478761 from polymeric implants in vivo.
  • To investigate EMD478761 efficacy in chick chorioallantoic membrane (CAM) and rat laser-induced choroidal neovascularization (CNV) models.

Main Methods:

  • Polyvinyl alcohol implants were designed for sustained release of EMD478761.
  • Angiogenesis was induced with basic fibroblast growth factor (bFGF) in CAM assays.
  • Choroidal neovascularization (CNV) was induced using diode laser in Brown-Norway rats.
  • EMD478761 or sham implants were administered intravitreally, and neovascular areas were quantified.

Main Results:

  • Sustained EMD478761 delivery significantly inhibited bFGF-induced angiogenesis in CAM without toxicity.
  • Intravitreal EMD478761 implants significantly suppressed laser-induced CNV in rats by 63% (P < 0.05).
  • HPLC confirmed in vitro release rates of EMD478761 from implants.

Conclusions:

  • Sustained delivery of EMD478761 exhibits potent in vivo antiangiogenic properties.
  • EMD478761 implants demonstrate efficacy in preclinical models of neovascularization.
  • These findings support the potential therapeutic benefit of EMD478761 implants for neovascular ocular diseases.

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