CCR3 is a target for age-related macular degeneration diagnosis and therapy

Nature. 2009 Jul 9;460(7252):225-30. doi: 10.1038/nature08151. Epub 2009 Jun 14.


Age-related macular degeneration (AMD), a leading cause of blindness worldwide, is as prevalent as cancer in industrialized nations. Most blindness in AMD results from invasion of the retina by choroidal neovascularisation (CNV). Here we show that the eosinophil/mast cell chemokine receptor CCR3 is specifically expressed in choroidal neovascular endothelial cells in humans with AMD, and that despite the expression of its ligands eotaxin-1, -2 and -3, neither eosinophils nor mast cells are present in human CNV. Genetic or pharmacological targeting of CCR3 or eotaxins inhibited injury-induced CNV in mice. CNV suppression by CCR3 blockade was due to direct inhibition of endothelial cell proliferation, and was uncoupled from inflammation because it occurred in mice lacking eosinophils or mast cells, and was independent of macrophage and neutrophil recruitment. CCR3 blockade was more effective at reducing CNV than vascular endothelial growth factor A (VEGF-A) neutralization, which is in clinical use at present, and, unlike VEGF-A blockade, is not toxic to the mouse retina. In vivo imaging with CCR3-targeting quantum dots located spontaneous CNV invisible to standard fluorescein angiography in mice before retinal invasion. CCR3 targeting might reduce vision loss due to AMD through early detection and therapeutic angioinhibition.

Publication types

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

MeSH terms

  • Animals
  • Cell Movement
  • Cell Proliferation
  • Cells, Cultured
  • Chemokine CCL11 / antagonists & inhibitors
  • Chemokine CCL11 / metabolism
  • Chemokine CCL24 / antagonists & inhibitors
  • Chemokine CCL24 / metabolism
  • Chemokine CCL26
  • Chemokines, CC / antagonists & inhibitors
  • Chemokines, CC / metabolism
  • Choroid / blood supply
  • Choroid / cytology
  • Choroid / metabolism
  • Choroidal Neovascularization / diagnosis
  • Choroidal Neovascularization / metabolism
  • Disease Models, Animal
  • Endothelial Cells / cytology
  • Endothelial Cells / metabolism
  • Humans
  • Inflammation
  • Leukocytes
  • Ligands
  • Macular Degeneration / diagnosis*
  • Macular Degeneration / metabolism
  • Macular Degeneration / therapy*
  • Mice
  • Mice, Inbred C57BL
  • Quantum Dots
  • Receptors, CCR3 / analysis
  • Receptors, CCR3 / antagonists & inhibitors*
  • Receptors, CCR3 / genetics
  • Receptors, CCR3 / immunology
  • Receptors, CCR3 / metabolism*
  • Retina / drug effects
  • Retina / pathology
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Vascular Endothelial Growth Factor A / immunology


  • CCL26 protein, human
  • CCR3 protein, human
  • Ccr3 protein, mouse
  • Chemokine CCL11
  • Chemokine CCL24
  • Chemokine CCL26
  • Chemokines, CC
  • Ligands
  • Receptors, CCR3
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A