April 2009
Volume 50, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2009
Induction of CD200 Signalling Reduces Inflammatory Cell Infiltration and Inhibits Laser-induced Choroidal Neovascularization
Author Affiliations & Notes
  • S. J. Robbie
    Molecular Therapy, UCL Institute of Ophthalmology, London, United Kingdom
  • S. E. Barker
    Molecular Therapy, UCL Institute of Ophthalmology, London, United Kingdom
  • D. A. Copland
    Department of Clinical Science, University of Bristol, Bristol, United Kingdom
  • J. Phillips
    Molecular Therapy, SP Biopharma, Palo Alto, California
  • Y. Duran
    Molecular Therapy, UCL Institute of Ophthalmology, London, United Kingdom
  • H. V. Tran
    Molecular Therapy, UCL Institute of Ophthalmology, London, United Kingdom
  • A. J. Smith
    Molecular Therapy, UCL Institute of Ophthalmology, London, United Kingdom
  • R. R. Ali
    Molecular Therapy, UCL Institute of Ophthalmology, London, United Kingdom
  • A. D. Dick
    Department of Clinical Science, University of Bristol, Bristol, United Kingdom
  • J. W. B. Bainbridge
    Molecular Therapy, UCL Institute of Ophthalmology, London, United Kingdom
  • Footnotes
    Commercial Relationships  S.J. Robbie, None; S.E. Barker, None; D.A. Copland, None; J. Phillips, SP Biopharma, E; Y. Duran, None; H.V. Tran, None; A.J. Smith, None; R.R. Ali, None; A.D. Dick, None; J.W.B. Bainbridge, None.
  • Footnotes
    Support  NIHR Biomedical Research Centre for Ophthalmology
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 3759. doi:
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      S. J. Robbie, S. E. Barker, D. A. Copland, J. Phillips, Y. Duran, H. V. Tran, A. J. Smith, R. R. Ali, A. D. Dick, J. W. B. Bainbridge; Induction of CD200 Signalling Reduces Inflammatory Cell Infiltration and Inhibits Laser-induced Choroidal Neovascularization. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3759.

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

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Abstract

Purpose: : The manipulation of macrophages in choroidal neovascularisation (CNV) offers a new strategy for therapeutic intervention in AMD. Macrophage activation and recruitment is suppressed by ligation of their CD200 receptors. The purpose of this study was to characterise the effect of CD200 signalling on macrophage activation and angiogenesis in a mouse model of laser-induced CNV.

Methods: : We administered an agonist monoclonal rat anti-mouse CD200R antibody (DX109) to adult C57BL/6 mice intravitreally 3 days following induction of CNV using diode laser. We measured the effect of DX109 on the size and permeablility of the induced CNV by digital image analysis of fundus fluorescein angiograms. We investigated its effect on inflammatory cell populations in the choroid and retina by fluorescence immunohistochemistry and flow cytometry.

Results: : Intravitreal delivery of DX109 was associated with a significant reduction in the number of CD11b positive cells present in the neurosensory retina 1 week following laser induction of CNV.Intravitreal delivery of DX109 following laser-injury resulted in a 43% reduction in the extent of CNV 2 weeks after laser-injury (p<0.05). We detected no change in the degree of vascular permeability as indicated by the extent of fluorescein leakage.

Conclusions: : Induction of CD200 signalling reduces the population of inflammatory cells present in the neurosensory retina following laser injury of Bruch’s membrane and reduces the extent of induced CNV. These findings suggest that manipulation of CD200 signalling may offer a new therapeutic approach to control pathological angiogenesis in the eye.

Keywords: choroid: neovascularization • immunomodulation/immunoregulation • inflammation 
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