Blockade of Sphingosine-1- Phosphate Reduces Macrophage Influx and Retinal and Choroidal Neovascularization

X. I.E. Bing, Jikui Shen, Aling Dong, Aymen Rashid, Glenn Stoller, Peter A. Campochiaro

Research output: Contribution to journalArticle

Abstract

Sphingosine-1-phosphate (SIP) is a bioactive lipid molecule that stimulates endothelial cell migration, proliferation, and survival in vitro, and tumor angiogenesis in vivo. In this study, we used a humanized monoclonal antibody (sonepcizumab) that selectively binds SIP to investigate its role in retinal and choroidal neovascularization (NV). Intraocular injection of sonepcizumab significantly reduced macrophage influx into ischemic retina and strongly suppressed retinal NV in mice with oxygen-induced ischemic retinopathy. In mice with laser-induced rupture sites in Bruch's membrane, intraocular injection of sonepcizumab significantly reduced the area of choroidal NVand concomitantly reduced fluorescein leakage from the remaining choroidal NV. Four weeks after intraocular injection of up to I.8 mg of the sonepcizumab in non-human primates, electroretinograms and fluorescein angiograms were normal, and light microscopy of ocular sections showed no evidence of structural damage. These data show for the first time that SIP stimulates both choroidal and retinal NV and suggest that sonepcizumab could be considered for evaluation in patients with choroidal or retinal NV.

Original languageEnglish (US)
Pages (from-to)192-198
Number of pages7
JournalJournal of Cellular Physiology
Volume218
Issue number1
DOIs
StatePublished - Jan 1 2009

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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