期刊
EMBO MOLECULAR MEDICINE
卷 5, 期 11, 页码 1775-1793出版社
WILEY
DOI: 10.1002/emmm.201302692
关键词
age-related macular disease; chemokines; monocyte; neurodegeneration; neuroinflammation
资金
- INSERM
- ANR blanc [AO5120DD]
- ANR Maladies Neurologiques et Psychiatriques [ANR-08-MNPS-003]
- ANR Geno [R09099DS]
- ANR Programme Emergence [ANR-EMMA-050]
- ERC starting Grant [ERC-2007 St.G. 210345]
- Assistance Publique-Hopitaux de Paris
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据