March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
CCL2/CCR2 Chemokine Axis Mediates Inflammatory Monocytes Recruitment To Lesions Of Atrophic Age-related Macular Degeneration And Retinal Degeneration In Cx3cr1 Deficient Mice
Author Affiliations & Notes
  • Florian Sennlaub
    Institut de la Vision, UMRS 986, University Pierre et Marie Curie, Paris, France
    Ophthalmology, Hotel Dieu, Paris, France
  • Constance Auvynet
    Laboratoire d'Immunologie Cellulaire, Inserm UMRS 945, Paris, France
  • Xavier Guillonneau
    Institut de la Vision, UMRS 986, University Pierre et Marie Curie, Paris, France
  • Serge Camelo
    Institut de la Vision, UMRS 986, University Pierre et Marie Curie, Paris, France
  • Sophie Lavalette
    Institut de la Vision, UMRS 986, University Pierre et Marie Curie, Paris, France
  • Jean-Louis Bourges
    Ophthalmology, Hotel Dieu, Paris, France
  • Francine Behar-Cohen
    Ophthalmology, Hotel Dieu, Paris, France
  • William Raoul
    Institut de la Vision, UMRS 986, University Pierre et Marie Curie, Paris, France
  • Christoph Combadiere
    Laboratoire d'Immunologie Cellulaire, Inserm UMRS 945, Paris, France
  • Footnotes
    Commercial Relationships  Florian Sennlaub, None; Constance Auvynet, None; Xavier Guillonneau, None; Serge Camelo, None; Sophie Lavalette, None; Jean-Louis Bourges, None; Francine Behar-Cohen, None; William Raoul, None; Christoph Combadiere, None
  • Footnotes
    Support  ERC-2007 St.G. 210345; ANR- 08-MNPS -003 LSHB-CT-2005-518167
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 1230. doi:
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      Florian Sennlaub, Constance Auvynet, Xavier Guillonneau, Serge Camelo, Sophie Lavalette, Jean-Louis Bourges, Francine Behar-Cohen, William Raoul, Christoph Combadiere; CCL2/CCR2 Chemokine Axis Mediates Inflammatory Monocytes Recruitment To Lesions Of Atrophic Age-related Macular Degeneration And Retinal Degeneration In Cx3cr1 Deficient Mice. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1230.

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

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Abstract
 
Purpose:
 

The chemokine/chemokine receptor axis CCL2/CCR2 has been shown to mediate inflammatory monocyte recruitment in a number of neurodegenerative disorders. Intraocular CCL2 levels are increased in wet AMD. We have shown that subretinal macrophages/microglial cells (Mφ/MCs) accumulation in Cx3cr1-/- mice is associated with photoreceptor degeneration. We here investigated intraocular CCL2 expression and CCR2+ inflammatory monocyte recruitment in Geographic Atrophy (GA) and Cx3cr1-/- mice and their influence on photoreceptor degeneration in Cx3cr1-/- mice.

 
Methods:
 

[CCL2] was measured by ELISA in aqueous humors of 18 GA patients and 22 age-matched control patients with no signs of AMD undergoing cataract surgery. CCL2 expression and the number of CCR2+inflammatory monocytes were analyzed in macular sections of donor tissues with GA lesions (n=8) and age matched control eyes (n=5). CCL2 expression (rt-PCR and ELISA) and inflammatory monocyte infiltration (cytometrie) was analyzed in light-injured Ccl2-/-, Cx3cr1-/- and Ccl2-/-Cx3cr1-/- mice. The influence of inflammatory monocyte infiltration on subretinal Mφ/MC accumulation and photoreceptor degeneration was analyzed using clodronate liposomes and CCR2 inhibitors.

 
Results:
 

We show that atrophic age-related macular disease (AMD) is associated with increased intraocular CCL2 levels and subretinal CCR2+ "inflammatory" monocyte infiltration. Using the Cx3cr1-/- mouse model of subretinal Mφ/MC accumulation and photoreceptor degeneration, we show that pharmacological inhibition of CCR2, genetic deletion of CCL2, and depletion of circulating monocytes prevents inflammatory monocyte recruitment, MC/Mφ accumulation, and photoreceptor degeneration in vivo. Our data suggests that CCL2/CCR2 inhibition represents a powerful tool for controlling inflammation and neurodegeneration in AMD.

 
Conclusions:
 

Our data suggests that CCL2/CCR2 inhibition represents a powerful tool for controlling subretinal inflammation and neurodegeneration in AMD.

 
Keywords: cytokines/chemokines • inflammation • photoreceptors 
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