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Journal articles
CX3CR1-dependent subretinal microglia cell accumulation is associated with cardinal features of age-related macular degeneration.
Christophe Combadière
1, 2, *
Charles Feumi
3
William Raoul
3
Nicole Keller
3
Mathieu Rodéro
1
Adeline Pézard
1
Sophie Lavalette
3
Marianne Houssier
3
Laurent Jonet
3
Emilie Picard
3
Patrice Debré
1, 2
Mirna Sirinyan
4
Philippe Deterre
1
Tania Ferroukhi
1
Salomon-Yves Cohen
5
Dominique Chauvaud
6
Jean-Claude Jeanny
3
Sylvain Chemtob
4
Francine Behar-Cohen
3, 6
Florian Sennlaub
3, *
*
Corresponding author
Christophe Combadière 1, 2
Correspondent author IdHAL : christophe-combadiere ResearcherId : http://www.researcherid.com/rid/I-5639-2013 ORCID : https://orcid.org/0000-0002-1755-4531
Charles Feumi 3
Author
William Raoul 3
Author IdHAL : william-raoul
Nicole Keller 3
Author
Mathieu Rodéro 1
Author IdHAL : mathieu-rodero ORCID : https://orcid.org/0000-0002-1300-0187
Adeline Pézard 1
Author
Sophie Lavalette 3
Author
Marianne Houssier 3
Author
Laurent Jonet 3
Author
Emilie Picard 3
Author IdHAL : emilie-picard
Patrice Debré 1, 2
Author
Mirna Sirinyan 4
Author
Philippe Deterre 1
Author
Tania Ferroukhi 1
Author
Salomon-Yves Cohen 5
Author
Dominique Chauvaud 6
Author
Jean-Claude Jeanny 3
Author
Sylvain Chemtob 4
Author
Francine Behar-Cohen 3, 6
Author
Florian Sennlaub 3
Correspondent author
1
Immunologie cellulaire et tissulaire (Gh Pitie-Salpetriere 83, Boulevard de L'Hopital 75013 PARIS - France)
- UPMC - Université Pierre et Marie Curie - Paris 6 (4 place Jussieu - 75005 Paris - France)
- IFR113 (France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U543 (101, rue de Tolbiac, 75013 Paris - France)
2
Service d'immunologie [CHU Pitié-Salpétrière] (47-83, boulevard de l'Hôpital 75651 PARIS Cedex 13 - France)
- AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP) (France)
- CHU Pitié-Salpêtrière [AP-HP] (47-83 Boulevard de l'Hôpital, 75013 Paris - France)
- Sorbonne Université (France)
- AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP) (France)
3
CRC (UMR_S 872) - Centre de Recherche des Cordeliers (CRBM des Cordeliers 15, rue de l'ecole de medecine batiment E 75270 Paris cedex 06 - France)
- UPMC - Université Pierre et Marie Curie - Paris 6 (4 place Jussieu - 75005 Paris - France)
- UPD5 - Université Paris Descartes - Paris 5 : U872 (12, rue de l'École de Médecine - 75270 Paris cedex 06 - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U872 (101, rue de Tolbiac, 75013 Paris - France)
- CNRS - Centre National de la Recherche Scientifique : UMR 872 (France)
4
Department of Pediatrics, Ophthalmology and Pharmacology (Montréal, Québec - Canada)
- Hôpital Sainte-Justine (France)
5
Centre d'Angiographie et de Laser (France)
6
Service d'ophtalmologie [Hôtel-Dieu - Paris] (Paris - France)
- AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP) (France)
- Hôtel-Dieu (France)
Abstract : The role of retinal microglial cells (MCs) in age-related macular degeneration (AMD) is unclear. Here we demonstrated that all retinal MCs express CX3C chemokine receptor 1 (CX3CR1) and that homozygosity for the CX3CR1 M280 allele, which is associated with impaired cell migration, increases the risk of AMD. In humans with AMD, MCs accumulated in the subretinal space at sites of retinal degeneration and choroidal neovascularization (CNV). In CX3CR1-deficient mice, MCs accumulated subretinally with age and albino background and after laser impact preceding retinal degeneration. Raising the albino mice in the dark prevented both events. The appearance of lipid-bloated subretinal MCs was drusen-like on funduscopy of senescent mice, and CX3CR1-dependent MC accumulation was associated with an exacerbation of experimental CNV. These results show that CX3CR1-dependent accumulation of subretinal MCs evokes cardinal features of AMD. These findings reveal what we believe to be a novel pathogenic process with important implications for the development of new therapies for AMD.
Document type :
Journal articles
Complete list of metadata
https://www.hal.inserm.fr/inserm-00176389
Contributor : Florian Sennlaub <>
Submitted on : Wednesday, October 3, 2007 - 2:24:16 PM
Last modification on : Tuesday, January 5, 2021 - 3:40:45 AM
Long-term archiving on: : Thursday, September 27, 2012 - 12:41:35 PM
Contributor : Florian Sennlaub <>
Submitted on : Wednesday, October 3, 2007 - 2:24:16 PM
Last modification on : Tuesday, January 5, 2021 - 3:40:45 AM
Long-term archiving on: : Thursday, September 27, 2012 - 12:41:35 PM
Identifiers
- HAL Id : inserm-00176389, version 1
- DOI : 10.1172/JCI31692
- PUBMED : 17909628
Collections
INSERM | UNIV-PARIS5 | UPMC | CORDELIERS | USPC | CNRS | SORBONNE-UNIVERSITE | SU-SCIENCES | UNIV-PARIS | SU-TI | UDL
Citation
Christophe Combadière, Charles Feumi, William Raoul, Nicole Keller, Mathieu Rodéro, et al.. CX3CR1-dependent subretinal microglia cell accumulation is associated with cardinal features of age-related macular degeneration.. Journal of Clinical Investigation, American Society for Clinical Investigation, 2007, 117 (10), pp.2920-2928. ⟨10.1172/JCI31692⟩. ⟨inserm-00176389⟩
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