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VEGF‐TRAP R1R2 suppresses choroidal neovascularization and VEGF‐induced breakdown of the blood–retinal barrier
Author(s) -
Saishin Yoshitsugu,
Saishin Yumiko,
Takahashi Kyoichi,
Silva Raquel Lima e,
Hylton Donna,
Rudge John S.,
Wiegand Stanley J.,
Campochiaro Peter A.
Publication year - 2003
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.10246
Subject(s) - choroidal neovascularization , neovascularization , vascular endothelial growth factor , vascular permeability , retinal , blood–retinal barrier , angiogenesis , vascular endothelial growth factor a , cancer research , chemistry , ophthalmology , medicine , diabetic retinopathy , microbiology and biotechnology , biology , pathology , endocrinology , vegf receptors , diabetes mellitus
Vascular endothelial growth factor (VEGF) plays a central role in the development of retinal neovascularization and diabetic macular edema. There is also evidence suggesting that VEGF is an important stimulator for choroidal neovascularization. In this study, we investigated the effect of a specific inhibitor of VEGF, VEGF‐TRAP R1R2 , in models for these disease processes. VEGF‐TRAP R1R2 is a fusion protein, which combines ligand binding elements taken from the extracellular domains of VEGF receptors 1 and 2 fused to the Fc portion of IgG1. Subcutaneous injections or a single intravitreous injection of VEGF‐TRAP R1R2 strongly suppressed choroidal neovascularization in mice with laser‐induced rupture of Bruch's membrane. Subcutaneous injection of VEGF‐TRAP R1R2 also significantly inhibited subretinal neovascularization in transgenic mice that express VEGF in photoreceptors. In two models of VEGF‐induced breakdown of the blood–retinal barrier (BRB), one in which recombinant VEGF is injected into the vitreous cavity and one in which VEGF expression is induced in the retina in transgenic mice, VEGF‐TRAP R1R2 significantly reduced breakdown of the BRB. These data confirm that VEGF is a critical stimulus for the development of choroidal neovascularization and indicate that VEGF‐TRAP R1R2 may provide a new agent for consideration for treatment of patients with choroidal neovascularization and diabetic macular edema. © 2003 Wiley‐Liss, Inc.