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CCR2+ monocytes infiltrate atrophic lesions in age-related macular disease and mediate photoreceptor degeneration in experimental subretinal inflammation in Cx3cr1 deficient mice
- Source :
- EMBO Molecular Medicine, Embo Molecular Medicine, 5(11), 1775-1793. Wiley-Blackwell, EMBO Molecular Medicine, 2013, 5 (11), pp.1775-93. ⟨10.1002/emmm.201302692⟩, EMBO Molecular Medicine, Wiley Open Access, 2013, 5 (11), pp.1775-93. ⟨10.1002/emmm.201302692⟩, Embo Molecular Medicine, vol. 5, pp. 1775-1793, EMBO Molecular Medicine, Wiley Open Access, 2013, 5 (11), pp.1775-93. 〈10.1002/emmm.201302692〉, Sennlaub, F, Auvynet, C, Calippe, B, Lavalette, S, Poupel, L, Hu, S J, Dominguez, E, Camelo, S, Levy, O, Guyon, E, Saederup, N, Charo, IF, van Rooijen, N, Nandrot, E, Bourges, J L, Behar-Cohen, F, Sahel, J A, Guillonneau, X, Raoul, W & Combadiere, C 2013, ' CCR2(+) monocytes infiltrate atrophic lesions in age-related macular disease and mediate photoreceptor degeneration in experimental subretinal inflammation in Cx3cr1 deficient mice ', Embo Molecular Medicine, vol. 5, no. 11, pp. 1775-1793 . https://doi.org/10.1002/emmm.201302692
- Publication Year :
- 2013
- Publisher :
- Blackwell Publishing Ltd, 2013.
-
Abstract
- International audience; Atrophic age-related macular degeneration (AMD) is associated with the subretinal accumulation of mononuclear phagocytes (MPs). Their role in promoting or inhibiting retinal degeneration is unknown. We here show that atrophic AMD is associated with increased intraocular CCL2 levels and subretinal CCR2(+) inflammatory monocyte infiltration in patients. Using age- and light-induced subretinal inflammation and photoreceptor degeneration in Cx3cr1 knockout mice, we show that subretinal Cx3cr1 deficient MPs overexpress CCL2 and that both the genetic deletion of CCL2 or CCR2 and the pharmacological inhibition of CCR2 prevent inflammatory monocyte recruitment, MP accumulation and photoreceptor degeneration in vivo. Our study shows that contrary to CCR2 and CCL2, CX3CR1 is constitutively expressed in the retina where it represses the expression of CCL2 and the recruitment of neurotoxic inflammatory CCR2(+) monocytes. CCL2/CCR2 inhibition might represent a powerful tool for controlling inflammation and neurodegeneration in AMD.
- Subjects :
- Retinal degeneration
Male
Pathology
CCR2
Chemokine
genetic structures
animal diseases
chemokines
Monocytes
age-related macular disease
neuroinflammation
Macular Degeneration
Mice
0302 clinical medicine
[ SDV.IMM ] Life Sciences [q-bio]/Immunology
Research Articles
Chemokine CCL2
Mice, Knockout
0303 health sciences
biology
neurodegeneration
medicine.anatomical_structure
Neutrophil Infiltration
[SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs
[ SDV.MHEP.OS ] Life Sciences [q-bio]/Human health and pathology/Sensory Organs
monocyte
Molecular Medicine
[SDV.IMM]Life Sciences [q-bio]/Immunology
Female
Receptors, Chemokine
medicine.symptom
Photoreceptor Cells, Vertebrate
medicine.medical_specialty
[SDV.IMM] Life Sciences [q-bio]/Immunology
Receptors, CCR2
CX3C Chemokine Receptor 1
Inflammation
CCL2
03 medical and health sciences
parasitic diseases
medicine
Animals
Humans
[SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs
030304 developmental biology
Retina
business.industry
Monocyte
Macular degeneration
medicine.disease
eye diseases
Mice, Inbred C57BL
030221 ophthalmology & optometry
biology.protein
sense organs
business
Subjects
Details
- Language :
- English
- ISSN :
- 17574684 and 17574676
- Volume :
- 5
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- EMBO Molecular Medicine
- Accession number :
- edsair.doi.dedup.....71bfc2b15eff5c7d3ba54f92f5e4e8fc