April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
In vivo Phenotyping Reveals That the Age-Related Retinal Degeneration in Ccl2/Cx3cr1 Double Knockout Mice Is Focal and Closely Associated With Inner Retinal Autofluorescent Lesions
U. F. Luhmann; S. Robbie; P. M. G. Munro; V. Luong; T. Jingsheng; F. W. Fitzke; R. E. MacLaren; J. W. Bainbridge; C.-C. Chan; R. R. Ali
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
  • V. Luong
    Department of Visual Science,
    UCL Institute of Ophthalmology, London, United Kingdom
  • T. Jingsheng
    Immunopathol Section, Lab of Immunology, National Eye Institute/NIH, Bethesda, Maryland
  • F. W. Fitzke
    Department of Visual Science,
    UCL Institute of Ophthalmology, London, United Kingdom
  • R. E. MacLaren
    Department of Genetics,
    UCL Institute of Ophthalmology, London, United Kingdom
    Nuffield Laboratory of Ophthalmology, University of Oxford, Oxford, United Kingdom
  • J. W. Bainbridge
    Department of Genetics,
    UCL Institute of Ophthalmology, London, United Kingdom
    NIHR Biomedical Research Center for Ophthalmology, London, United Kingdom
  • C.-C. Chan
    Immunopathol Section, Lab of Immunology, National Eye Institute/NIH, Bethesda, Maryland
  • R. R. Ali
    Department of Genetics,
    UCL Institute of Ophthalmology, London, United Kingdom
    NIHR Biomedical Research Center for Ophthalmology, London, United Kingdom
  • Footnotes
    Commercial Relationships  U.F. Luhmann, None; S. Robbie, None; P.M.G. Munro, None; V. Luong, None; T. Jingsheng, None; F.W. Fitzke, None; R.E. MacLaren, None; J.W. Bainbridge, None; C.-C. Chan, None; R.R. Ali, None.
  • Footnotes
    Support  NIHR Biomedical Research Centre for Ophthalmology, MRC G0801004
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 6138. doi:
  • Views
  • Share
  • Tools
    • Alerts
      User Alerts
      You are adding an alert for:
      In vivo Phenotyping Reveals That the Age-Related Retinal Degeneration in Ccl2/Cx3cr1 Double Knockout Mice Is Focal and Closely Associated With Inner Retinal Autofluorescent Lesions
      You will receive an email whenever this article is corrected, updated, or cited in the literature. You can manage this and all other alerts in My Account
      The alert will be sent to:
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation
      Citation

      U. F. Luhmann, S. Robbie, P. M. G. Munro, V. Luong, T. Jingsheng, F. W. Fitzke, R. E. MacLaren, J. W. Bainbridge, C.-C. Chan, R. R. Ali; In vivo Phenotyping Reveals That the Age-Related Retinal Degeneration in Ccl2/Cx3cr1 Double Knockout Mice Is Focal and Closely Associated With Inner Retinal Autofluorescent Lesions. Invest. Ophthalmol. Vis. Sci. 2010;51(13):6138.

      Download citation file:

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

      ×
    • Get Permissions
  • Supplements
Abstract

Purpose: : Microglia/macrophage activation and migration in the retina plays an important role in age-related macular degeneration (AMD) and are both controlled by cytokine signaling pathways. CX3CR1 receptor polymorphisms are associated with an increased risk to develop AMD and Cx3cr1 knockout mice show a late onset retinal degeneration, while senescent (>2 years) C-C cytokine 2 (Ccl2) knockout mice do not. Double knockout mice for both genes (CCDKO) develop an accelerated, early onset and more severe retinal phenotype compared to either of the single knockout mice. To understand the interaction of Ccl2 and Cx3cr1 signaling we assessed the progression of the age-related retinal phenotype in CCDKO mice in vivo.

Methods: : CCDKO and aged-matched wildtype mice were kept under 12 h dark/light cycle and degenerative and vascular phenotypes were assessed at 1, 4 ,8 and 12 month of age using autofluorescent scanning laser ophthalmoscopy (AF-SLO), optical coherence tomography (OCT) and fundus fluorescein angiography (FFA).

Results: : By AF-SLO we identified two types of autofluorescent lesions in CCDKO mice from the age of 1 month onwards. Subretinal lesions were distributed evenly across the fundus whereas inner retinal lesions were mainly localized to the inferior retina and preceded an associated retinal degeneration and an increasing level of low grade vascular leakiness with tortuous vessels in the same area.

Conclusions: : Our data suggest the described progressive retinal degeneration of CCDKO mice is more localized to the inferior retina and might be triggered by an external factor such as light. We propose that light-induced outer retinal damage may lead to inner retinal responses, possibly defective microglia leading to microglia-induced retinal degeneration, which may contribute to the pathogenesis of AMD.

Keywords: age-related macular degeneration • cytokines/chemokines • microglia 
© 2010, 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.
×
×

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.

×
This site uses cookies. By continuing to use our website, you are agreeing to our privacy policy.Accept