April 2009
Volume 50, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2009
The Drusen-Like Phenotype in MCP-1/Ccl2 Knockout Mice Is Caused by an Accelerated Accumulation of Swollen Autofluorescent Subretinal Macrophages
U. F. Luhmann; S. Robbie; P. M. G. Munro; S. E. Barker; Y. Duran; V. Luong; F. W. Fitzke; J. W. B. Bainbridge; R. R. Ali; R. E. MacLaren
Author Affiliations & Notes
  • U. F. Luhmann
    Department of Genetics,
    UCL Institute of Ophthalmology, London, United Kingdom
  • S. Robbie
    Department of Genetics,
    UCL Institute of Ophthalmology, London, United Kingdom
  • P. M. G. Munro
    Imaging Unit,
    UCL Institute of Ophthalmology, London, United Kingdom
  • S. E. Barker
    Department of Genetics,
    UCL Institute of Ophthalmology, London, United Kingdom
  • Y. Duran
    Department of Genetics,
    UCL Institute of Ophthalmology, London, United Kingdom
  • V. Luong
    Laboratory for Physiological Optics,
    UCL Institute of Ophthalmology, London, United Kingdom
  • F. W. Fitzke
    Laboratory for Physiological Optics,
    UCL Institute of Ophthalmology, London, United Kingdom
  • J. W. B. Bainbridge
    Department of Genetics,
    UCL Institute of Ophthalmology, London, United Kingdom
  • R. R. Ali
    Department of Genetics,
    UCL Institute of Ophthalmology, London, United Kingdom
  • R. E. MacLaren
    Department of Genetics,
    UCL Institute of Ophthalmology, London, United Kingdom
    current address: Nuffield Laboratory of Ophthalmology, University of Oxford, Oxford, United Kingdom
  • Footnotes
    Commercial Relationships  U.F. Luhmann, None; S. Robbie, None; P.M.G. Munro, None; S.E. Barker, None; Y. Duran, None; V. Luong, None; F.W. Fitzke, None; J.W.B. Bainbridge, None; R.R. Ali, None; R.E. MacLaren, None.
  • Footnotes
    Support  NIHR Biomedical Research Centre for Ophthalmology; RCS of Edinburgh; Health Foundation
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 3756. doi:
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      U. F. Luhmann, S. Robbie, P. M. G. Munro, S. E. Barker, Y. Duran, V. Luong, F. W. Fitzke, J. W. B. Bainbridge, R. R. Ali, R. E. MacLaren; The Drusen-Like Phenotype in MCP-1/Ccl2 Knockout Mice Is Caused by an Accelerated Accumulation of Swollen Autofluorescent Subretinal Macrophages. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3756.

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Abstract

Purpose: : Drusen are clinical hallmarks of age related macular degeneration (AMD) the leading cause of blindness in the developed world. These extracellular deposits are located between the basal lamina of the retinal pigment epithelium (RPE) and Bruch's membrane (BM) and are visible in fundus images of patients as yellow opaque spots. MCP-1/Ccl2 knockout mice have been reported to develop drusen and phenotypic features that are similar to AMD including a higher susceptibility to CNV. Here we investigate the origin of these drusen in vivo and evaluate in detail MCP-1 mice as a model for AMD.

Methods: : Eyes of 2-25 month old MCP-1 and C57Bl/6 mice were assessed in vivo by autofluorescence scanning laser ophthalmoscopy (AF-SLO), electroretinography, laser-induced choroidal neovasculariszation (CNV) and fluorescein fundus angiography. Immunohistochemistry and quantitative histological and ultrastructural morphometry were applied.

Results: : The drusen-like phenotype of MCP-1 mice was correlated with an accelerated accumulation of autofluorescent foci in AF-SLO and CD68 positive, bloated cells in the subretinal space with age. These cells contained pigment granules and phagosomes with outer segment and lipofuscin inclusions that might explain their autofluorescence. Despite the accelerated accumulation of macrophages we observed only age-related RPE damage, photoreceptor loss and sub-RPE deposits that were similar in MCP-1 and wildtype mice. Furthermore, we observed a reduced susceptibility of MCP-1 mice to laser induced CNV.

Conclusions: : Our data suggest that the lack of MCP-1 leads to a monocyte/macrophage trafficking defect during aging and to an impaired recruitment of these cells to sites of laser injury. Other previously described AMD similar features of MCP-1 mice may be explained by normal age-related processes.

Keywords: age-related macular degeneration • aging • choroid: neovascularization 
© 2009, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Permission to republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Office prior to publication.
Copyright © 2025 Association for Research in Vision and Ophthalmology.
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