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Article
Nature Medicine  9, 1390 - 1397 (2003)
Published online: 19 October 2003; | doi:10.1038/nm950

An animal model of age-related macular degeneration in senescent Ccl-2- or Ccr-2-deficient mice

Jayakrishna Ambati1, Akshay Anand1, Stefan Fernandez2, Eiji Sakurai1, Bert C Lynn3, William A Kuziel4, Barrett J Rollins5 & Balamurali K Ambati6

1  Department of Ophthalmology, University of Kentucky, 740 South Limestone Street, Lexington, Kentucky 40536-0284, USA.

2  Department of Microbiology and Immunology, University of Kentucky, MS423 Medical Science Building, Lexington, Kentucky 40506-0286, USA.

3  Department of Chemistry, University of Kentucky, A053 ASTeCC Building, Lexington, Kentucky 40506-0286, USA.

4  Institute for Cellular and Molecular Biology, University of Texas, Austin, Texas 78712-1095, USA.

5  Dana Farber Cancer Institute, Brigham & Women's Hospital, Harvard Medical School, 44 Binney Street Mayer 430, Boston, Massachusetts 02115, USA.

6  Department of Ophthalmology, Medical College of Georgia, Augusta, Georgia 30907, USA.

Correspondence should be addressed to Jayakrishna Ambati jamba2@uky.edu
The study and treatment of age-related macular degeneration (AMD), a leading cause of blindness, has been hampered by a lack of animal models. Here we report that mice deficient either in monocyte chemoattractant protein-1 (Ccl-2; also known as MCP-1) or its cognate C-C chemokine receptor-2 (Ccr-2) develop cardinal features of AMD, including accumulation of lipofuscin in and drusen beneath the retinal pigmented epithelium (RPE), photoreceptor atrophy and choroidal neovascularization (CNV). Complement and IgG deposition in RPE and choroid accompanies senescence in this model, as in human AMD. RPE or choroidal endothelial production of Ccl-2 induced by complement C5a and IgG may mediate choroidal macrophage infiltration into aged wild-type choroids. Wild-type choroidal macrophages degrade C5 and IgG in eye sections of Ccl2-/- or Ccr2-/- mice. Impaired macrophage recruitment may allow accumulation of C5a and IgG, which induces vascular endothelial growth factor (VEGF) production by RPE, possibly mediating development of CNV. These models implicate macrophage dysfunction in AMD pathogenesis and may be useful as a platform for validating therapies.

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REFERENCE
Macular Degeneration, Age Related
Nature Encyclopaedia of Life Sciences

REVIEWS
Optical coherence tomography—a review of the principles and contemporary uses in retinal investigation
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NEWS AND VIEWS
Macrophages eyed in macular degeneration
Nature Medicine News and Views (01 Nov 2003)

RESEARCH
Towards an understanding of age-related macular disease
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Laboratory Investigation Article (01 Feb 2002)
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Nature Medicine
ISSN: 1078-8956
EISSN: 1546-170X
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