May 2004
Volume 45, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2004
An animal model of atrophic and neovascular age–related macular degeneration in Ccl2–/– or Ccr2–/– mice
Author Affiliations & Notes
  • J. Ambati
    Ophthalmology & Visual Sciences,
    University of Kentucky, Lexington, KY
  • A. Anand
    Ophthalmology & Visual Sciences,
    University of Kentucky, Lexington, KY
  • E. Sakurai
    Ophthalmology & Visual Sciences,
    University of Kentucky, Lexington, KY
  • S. Fernandez
    Microbiology, Immunology & Medical Genetics,
    University of Kentucky, Lexington, KY
  • B.J. Rollins
    Dana Farber Cancer Institute, Harvard Medical School, Boston, MA
  • W.A. Kuziel
    Institute for Cellular and Molecular Biology, University of Texas, Austin, TX
  • B.C. Lynn
    Chemistry,
    University of Kentucky, Lexington, KY
  • B.K. Ambati
    Ophthalmology, Medical College of Georgia, Augusta, GA
  • Footnotes
    Commercial Relationships  J. Ambati, University of Kentucky Research Foundation P; A. Anand, None; E. Sakurai, None; S. Fernandez, None; B.J. Rollins, None; W.A. Kuziel, None; B.C. Lynn, None; B.K. Ambati, None.
  • Footnotes
    Support  American Geriatrics Society,Foundation Fighting Blindness,Prevent Blindness America,Knights Templar
Investigative Ophthalmology & Visual Science May 2004, Vol.45, 3388. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      J. Ambati, A. Anand, E. Sakurai, S. Fernandez, B.J. Rollins, W.A. Kuziel, B.C. Lynn, B.K. Ambati; An animal model of atrophic and neovascular age–related macular degeneration in Ccl2–/– or Ccr2–/– mice . Invest. Ophthalmol. Vis. Sci. 2004;45(13):3388.

      Download citation file:


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

      ×
  • Supplements
Abstract

Abstract: : Purpose: To study the effect of macrophage recruitment deficiency in aged mice. Methods: Mice deficient either in monocyte chemoattractant protein–1 (Ccl–2) or its cognate C–C chemokine receptor–2 (Ccr–2) were studied over their lifespan by fundus, angiographic, ultrastructural, flow cytometric, and biochemical examination. The ability of wild–type choroidal macrophages to process and degrade aging–associated inflammatory debris was assayed in situ. The impact of inflammatory debris on neighboring cell production of Ccl–2 or vascular endothelial growth factor (VEGF) was assayed by cell culture studies. Results: Both Ccl2–/– and Ccr2–/– mice develop cardinal features of AMD, including 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 AMD. Complement C5a and IgG induced RPE or choroidal endothelial production of Ccl–2 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 accretion of C5a and IgG, which induce RPE production of vascular endothelial growth factor, possibly mediating CNV development. Conclusions: These models implicate macrophage dysfunction in AMD pathogenesis and may constitute a platform for validating therapies.

Keywords: age–related macular degeneration • retinal degenerations: cell biology • choroid: neovascularization 
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×