RT Journal Article SR Electronic T1 Vascular Targeting of Ocular Neovascularization with a Vascular Endothelial Growth Factor121/Gelonin Chimeric Protein JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 1543 OP 1550 DO 10.1124/mol.105.015628 VO 68 IS 6 A1 Hideo Akiyama A1 Khalid A. Mohamedali A1 Raquel Lima e Silva A1 Shu Kachi A1 JiKui Shen A1 Christina Hatara A1 Naoyasu Umeda A1 Sean F. Hackett A1 Sadia Aslam A1 Melissa Krause A1 Hong Lai A1 Michael G. Rosenblum A1 Peter A. Campochiaro YR 2005 UL http://molpharm.aspetjournals.org/content/68/6/1543.abstract AB 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.