RGD Reference Report - CCR2(+) monocytes infiltrate atrophic lesions in age-related macular disease and mediate photoreceptor degeneration in experimental subretinal inflammation in Cx3cr1 deficient mice. - Rat Genome Database

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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.

Authors: Sennlaub, F  Auvynet, C  Calippe, B  Lavalette, S  Poupel, L  Hu, SJ  Dominguez, E  Camelo, S  Levy, O  Guyon, E  Saederup, N  Charo, IF  Rooijen, NV  Nandrot, E  Bourges, JL  Behar-Cohen, F  Sahel, JA  Guillonneau, X  Raoul, W  Combadiere, C 
Citation: Sennlaub F, etal., EMBO Mol Med. 2013 Nov;5(11):1775-93. doi: 10.1002/emmm.201302692. Epub 2013 Oct 21.
RGD ID: 8661224
Pubmed: PMID:24142887   (View Abstract at PubMed)
PMCID: PMC3840491   (View Article at PubMed Central)
DOI: DOI:10.1002/emmm.201302692   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Geographic Atrophy  IEP 8661224protein:increased expression:aqueous humor of eyeballRGD 
Geographic Atrophy  IEP 8661224protein:increased expression:monocyteRGD 
Geographic Atrophy  ISOCCL2 (Homo sapiens)8661224; 8661224protein:increased expression:aqueous humor of eyeballRGD 
Geographic Atrophy  ISOCCR2 (Homo sapiens)8661224; 8661224protein:increased expression:monocyteRGD 
macular degeneration  ISOCcl2 (Mus musculus)8661224mRNA and protein:increased expression:retinaRGD 
macular degeneration  ISOCcl2 (Mus musculus)8661224mRNA and protein:increased expression:retina:RGD 
macular degeneration  IEP 8661224mRNA and protein:increased expression:retinaRGD 
macular degeneration  IMP 8661224 RGD 
retinitis  ISOCcr2 (Mus musculus)8661224; 8661224 RGD 
retinitis  ISOCx3cr1 (Mus musculus)8661224; 8661224 RGD 
retinitis  IMP 8661224; 8661224 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ccl2  (C-C motif chemokine ligand 2)
Ccr2  (C-C motif chemokine receptor 2)
Cx3cr1  (C-X3-C motif chemokine receptor 1)

Genes (Mus musculus)
Ccl2  (C-C motif chemokine ligand 2)
Ccr2  (C-C motif chemokine receptor 2)
Cx3cr1  (C-X3-C motif chemokine receptor 1)

Genes (Homo sapiens)
CCL2  (C-C motif chemokine ligand 2)
CCR2  (C-C motif chemokine receptor 2)
CX3CR1  (C-X3-C motif chemokine receptor 1)

Objects referenced in this article
Gene CCL13 C-C motif chemokine ligand 13 Homo sapiens
Gene Ccl12 C-C motif chemokine ligand 12 Mus musculus
Gene Ccl12 C-C motif chemokine ligand 12 Rattus norvegicus

Additional Information