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

Atsunobu Takeda, 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 and Jayakrishna Ambati ()
Additional contact information
Atsunobu Takeda: Department of Ophthalmology & Visual Science,
Judit Z. Baffi: Department of Ophthalmology & Visual Science,
Mark E. Kleinman: Department of Ophthalmology & Visual Science,
Won Gil Cho: Department of Ophthalmology & Visual Science,
Miho Nozaki: Department of Ophthalmology & Visual Science,
Kiyoshi Yamada: Department of Ophthalmology & Visual Science,
Hiroki Kaneko: Department of Ophthalmology & Visual Science,
Romulo J. C. Albuquerque: Department of Ophthalmology & Visual Science,
Sami Dridi: Department of Ophthalmology & Visual Science,
Kuniharu Saito: Department of Ophthalmology & Visual Science,
Brian J. Raisler: Department of Ophthalmology & Visual Science,
Steven J. Budd: The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
Pete Geisen: The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
Ariel Munitz: Cincinnati Children’s Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio 45229, USA
Balamurali K. Ambati: Moran Eye Center, University of Utah School of Medicine, Salt Lake City, Utah 84132, USA
Martha G. Green: Department of Ophthalmology & Visual Science,
Tatsuro Ishibashi: Graduate School of Medical Sciences, Kyushu University
John D. Wright: The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
Alison A. Humbles: Children’s Hospital, Harvard Medical School, Boston, Massachusetts 02215, USA
Craig J. Gerard: Children’s Hospital, Harvard Medical School, Boston, Massachusetts 02215, USA
Yuichiro Ogura: Nagoya City University Graduate School of Medical Sciences
Yuzhen Pan: Casey Eye Institute, Oregon Health and Science University, Portland, Oregon 97239, USA
Justine R. Smith: Casey Eye Institute, Oregon Health and Science University, Portland, Oregon 97239, USA
Salvatore Grisanti: University of Luebeck
M. Elizabeth Hartnett: The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
Marc E. Rothenberg: Cincinnati Children’s Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio 45229, USA
Jayakrishna Ambati: Department of Ophthalmology & Visual Science,

Nature, 2009, vol. 460, issue 7252, 225-230

Abstract: 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.

Date: 2009
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DOI: 10.1038/nature08151

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