VEGF-TRAP(R1R2) suppresses choroidal neovascularization and VEGF-induced breakdown of the blood-retinal barrier

J Cell Physiol. 2003 May;195(2):241-8. doi: 10.1002/jcp.10246.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blood-Retinal Barrier / drug effects
  • Blood-Retinal Barrier / physiology
  • Choroid / drug effects
  • Choroid / metabolism
  • Choroid / physiopathology
  • Choroid Diseases / drug therapy*
  • Choroid Diseases / metabolism
  • Choroid Diseases / physiopathology
  • Diabetic Retinopathy / drug therapy*
  • Diabetic Retinopathy / metabolism
  • Diabetic Retinopathy / physiopathology
  • Disease Models, Animal
  • Endothelial Growth Factors / antagonists & inhibitors*
  • Endothelial Growth Factors / metabolism
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Lymphokines / antagonists & inhibitors*
  • Lymphokines / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / physiopathology
  • Receptors, Growth Factor / therapeutic use
  • Recombinant Fusion Proteins / pharmacology*
  • Recombinant Fusion Proteins / therapeutic use
  • Retina / drug effects
  • Retina / metabolism
  • Retina / physiopathology
  • Retinal Artery / drug effects
  • Retinal Artery / pathology
  • Retinal Artery / physiopathology
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors


  • Endothelial Growth Factors
  • Intercellular Signaling Peptides and Proteins
  • Lymphokines
  • Receptors, Growth Factor
  • Recombinant Fusion Proteins
  • VEGF Trap R1R2 protein
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors