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. 2003 Nov;9(11):1390-7.
doi: 10.1038/nm950. Epub 2003 Oct 19.

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

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

Jayakrishna Ambati et al. Nat Med. 2003 Nov.

Abstract

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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Comment in

  • Macrophages eyed in macular degeneration.
    Forrester JV. Forrester JV. Nat Med. 2003 Nov;9(11):1350-1. doi: 10.1038/nm1103-1350. Nat Med. 2003. PMID: 14595424 No abstract available.
  • Mouse models of visual deficits.
    Sengupta N, Caballero S. Sengupta N, et al. Nat Med. 2004 Jul;10(7):663; author reply 663. doi: 10.1038/nm0704-663a. Nat Med. 2004. PMID: 15229502 No abstract available.

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