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

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

Atsunobu Takeda ¹, Judit Z Baffi, Mark E Kleinman, Won Gil Cho, Miho Nozaki, Kiyoshi Yamada, Hiroki Kaneko, Romulo J C Albuquerque, Sami Dridi, Kuniharu Saito, Brian J Raisler, Steven J Budd, Pete Geisen, Ariel Munitz, Balamurali K Ambati, Martha G Green, Tatsuro Ishibashi, John D Wright, Alison A Humbles, Craig J Gerard, Yuichiro Ogura, Yuzhen Pan, Justine R Smith, Salvatore Grisanti, M Elizabeth Hartnett, Marc E Rothenberg, Jayakrishna Ambati

Affiliations

Affiliation

1 Department of Ophthalmology & Visual Science, University of Kentucky, Lexington, Kentucky 40506, USA.

PMID: 19525930 DOI: 10.1038/nature08151

Abstract

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.

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