RGD Reference Report - CCR3 is a target for age-related macular degeneration diagnosis and therapy. - Rat Genome Database

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

Authors: Takeda, A  Baffi, JZ  Kleinman, ME  Cho, WG  Nozaki, M  Yamada, K  Kaneko, H  Albuquerque, RJ  Dridi, S  Saito, K  Raisler, BJ  Budd, SJ  Geisen, P  Munitz, A  Ambati, BK  Green, MG  Ishibashi, T  Wright, JD  Humbles, AA  Gerard, CJ  Ogura, Y  Pan, Y  Smith, JR  Grisanti, S  Hartnett, ME  Rothenberg, ME  Ambati, J 
Citation: Takeda A, etal., Nature. 2009 Jul 9;460(7252):225-30. Epub 2009 Jun 14.
RGD ID: 6893454
Pubmed: PMID:19525930   (View Abstract at PubMed)
PMCID: PMC2712122   (View Article at PubMed Central)
DOI: DOI:10.1038/nature08151   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Choroidal Neovascularization  IEP 6893454associated with Macular DegenerationRGD 
Choroidal Neovascularization  ISOCcr3 (Mus musculus)6893454 RGD 
Choroidal Neovascularization  IMP 6893454 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ccr3  (C-C motif chemokine receptor 3)

Genes (Mus musculus)
Ccr3  (C-C motif chemokine receptor 3)

Genes (Homo sapiens)
CCR3  (C-C motif chemokine receptor 3)


Additional Information