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CCR3 is a target for age-related macular degeneration diagnosis and therapy
Open accessAbstract
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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“Elevated CCL11 in the plasma and cerebrospinal fluid seen in aging mice and humans are associated with declining neurogenesis, neurodegenerative disease, and cognitive decline and may contribute to driving neovascularisation in AMD via interaction with CCR3 [1, 93, 123].”
From Fecal microbiota transfer between young and aged mice reverses hallmarks of the aging gut, eye, and brain (2022) · cites this paper as [1]
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“Elevated CCL11 in the plasma and cerebrospinal fluid seen in aging mice and humans are associated with declining neurogenesis, neurodegenerative disease, and cognitive decline and may contribute to driving neovascularisation in AMD via interaction with CCR3 [1, 93, 123].”
From Fecal microbiota transfer between young and aged mice reverses hallmarks of the aging gut, eye, and brain (2022) · cites this paper as [1]
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Metadata
- Authors
- Takeda, A., Baffi, J. Z., Kleinman, M. E., Cho, W. G., Nozaki, M., Yamada, K., Kaneko, H., Albuquerque, R. J. C., Dridi, S., Saito, K., Raisler, B. J., Budd, S. J., Geisen, P., Munitz, A., Ambati, B. K., Green, M. G., Ishibashi, T., Wright, J. D., Humbles, A. A., Gerard, C. J., Ogura, Y., Pan, Y., Smith, J. R., Grisanti, S., Hartnett, M. E., Rothenberg, M. E., & Ambati, J.
- Affiliations
- University of Kentucky (US)
- University of North Carolina at Chapel Hill (US)
- Cincinnati Children's Hospital Medical Center (US)
- University of Utah (US)
- Kyushu University (JP)
- Harvard University (US)
- Nagoya City University (JP)
- Oregon Health & Science University (US)
- University of Lübeck (DE)
- Corresponding author
- Ambati, Jayakrishna
- ORCID
- Venue
- Nature
- Published
- 2009-06-14
- Volume
- 460
- Issue
- 7252
- Pages
- 225-230
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC2712122
- OpenAlex
- W1978268544
- Cited by
- 263
- References
- 49
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 10 · 2023: 8 · 2022: 18 · 2021: 11 · 2020: 12 · 2019: 11 · 2018: 10 · 2017: 20 · 2016: 22 · 2015: 14 · 2014: 20 · 2013: 22 · 2012: 22
- FWCI
- 23.93
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- UNC Libraries
- Funders
- U.S. Department of Defense
- American Health Assistance Foundation
- International Retinal Research Foundation
- Research to Prevent Blindness
- Macula Vision Research Foundation
- E. Matilda Ziegler Foundation for the Blind
- National Institutes of Health
- National Heart, Lung, and Blood Institute
- National Eye Institute (R01EY017950, R01EY018836, R01EY015422, EY018836, R01EY018350, EY018350, EY 010572, EY017011, R01EY017182, EY017182, EY017950, EY015130, R01EY017011, P30EY010572, EY015422)
- National Institute of Allergy and Infectious Diseases (R01AI039759, R37AI045898, AI 45898, AI039759)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK076893, DK076893)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
- Keywords
- age-related macular degeneration, CCR3, choroidal neovascularization, eotaxin, eosinophils, mast cells, endothelial cell proliferation, anti-VEGF therapy, early diagnosis, quantum dot imaging, retinal neovascularization, blindness prevention, anti-angiogenic therapy
- MeSH terms
- Chemokine CCL26, Animals, Cell Movement, Cells, Cultured, Choroid, Disease Models, Animal, Humans, Inflammation, Leukocytes, Ligands, Macular Degeneration, Mice, Inbred C57BL, Retina, Chemokines, CC, Choroidal Neovascularization, Vascular Endothelial Growth Factor A, Endothelial Cells, Quantum Dots, Cell Proliferation, Mice, Receptors, CCR3, Chemokine CCL11, Chemokine CCL24
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