Vascular targeting of ocular neovascularization with a vascular endothelial growth factor121/gelonin chimeric protein

Hideo Akiyama, Khalid A. Mohamedali, Raquel Lima E Silva, Shu Kachi, Ji Kui Shen, Christina Hatara, Naoyasu Umeda, Sean F. Hackett, Sadia Aslam, Melissa Krause, Hong Lai, Michael G. Rosenblum, Peter A. Campochiaro

Research output: Contribution to journalArticlepeer-review

Abstract

Tumors provide an extremely abnormal microenvironment that stimulates neovascularization from surrounding vessels and causes altered gene expression within vascular cells. Up-regulation of vascular endothelial growth factor (VEGF) receptors has allowed selective destruction of tumor vessels by administration of a chimeric protein consisting of VEGF121 coupled to the toxin gelonin (VEGF/rGel). We sought to determine whether there is sufficient up-regulation of VEGF receptors in endothelial cells participating in ocular neovascularization to permit a similar strategy. After intravenous injection of 45 mg/kg VEGF/rGel, but not uncoupled recombinant gelonin (rGel), there was immunofluorescent staining for rGel within choroidal neovascularization in mice and regression of the neovascularization occurred, demonstrating successful vascular targeting via the systemic circulation. Intraocular injection of 5 ng of VEGF/rGel also caused significant regression of choroidal neovascularization and regression of retinal neovascularization in two models, transgenic mice with expression of VEGF in photoreceptors and mice with ischemic retinopathy, whereas injection of 5 ng of rGel had no effect. These data suggest that the strategy of vascular targeting can be applied to nonmalignant neovascular diseases and could serve as the basis of a new treatment to reduce established ocular neovascularization.

Original languageEnglish (US)
Pages (from-to)1543-1550
Number of pages8
JournalMolecular Pharmacology
Volume68
Issue number6
DOIs
StatePublished - Dec 2005

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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