May 2003
Volume 44, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2003
An Animal Model of Age-related Macular Degeneration in Senescent Macrophage Recruitment Impaired Mice
Author Affiliations & Notes
  • J. Ambati
    Ophthalmology, University of Kentucky, Lexington, KY, United States
  • A. Anand
    Ophthalmology, University of Kentucky, Lexington, KY, United States
  • E. Sakurai
    Ophthalmology, University of Kentucky, Lexington, KY, United States
  • W.A. Kuziel
    Institute for Cellular and Molecular Biology, University of Texas, Austin, TX, United States
  • B.J. Rollins
    Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, United States
  • B.K. Ambati
    Ophthalmology, Medical College of Georgia, Augusta, GA, United States
  • Footnotes
    Commercial Relationships  J. Ambati, University of Kentucky P; Eyetech Pharmaceuticals R; A. Anand, None; E. Sakurai, None; W.A. Kuziel, None; B.J. Rollins, None; B.K. Ambati, None.
  • Footnotes
    Support  FFB Career Development Award, PBA/FFS Grant in Aid, U of KY Physician Scientist Award (JA)
Investigative Ophthalmology & Visual Science May 2003, Vol.44, 1718. doi:
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      J. Ambati, A. Anand, E. Sakurai, W.A. Kuziel, B.J. Rollins, B.K. Ambati; An Animal Model of Age-related Macular Degeneration in Senescent Macrophage Recruitment Impaired Mice . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1718.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Abstract: : Purpose: To characterize the development of age-related macular degeneration (AMD)-like pathology in senescent mice genetically deficient either in monocyte chemoattractant protein-1 (MCP-1) or its C-C chemokine receptor-2 (CCR2), and to dissect the molecular etiology of this phenotype. Methods: Wildtype, MCP-1 -/-, and CCR2 -/- deficient mice were examined from 0-24 months of age by fundus photography, indocyanine green angiography, immunohistochemistry, and transmission electron microscopy. Human retinal pigment epithelium (RPE) cells were exposed to protein deposits identified in knockout mice. Results: MCP-1 -/- and CCR2 -/- mice develop lipofuscin, thickening of Bruch’s membrane, drusenoid deposits, focal and diffuse RPE atrophy, and choroidal neovascularization in an age-related fashion. Deposition of complement component C5, immunoglobulin G (IgG), and advanced glycation endproducts (AGE) in the RPE accompanies senescence in these knockout mice as in patients with AMD. C5, IgG, and AGE induce human RPE cell production of MCP-1 and vascular endothelial growth factor (VEGF). Wildtype mice demonstrate increased expression of MCP-1 in the RPE as they age. Conclusions: Immune/inflammatory deposits that accumulate in senescent knockout mice stimulate RPE cells to produce MCP-1, suggesting that MCP-1/CCR2 deficiency prevents the normal clearance of these protein deposits, which in turn may contribute to the development of an AMD-like phenotype.

Keywords: age-related macular degeneration • animal model • inflammation 
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