CCR2(+) monocytes infiltrate atrophic lesions in age-related macular disease and mediate photoreceptor degeneration in experimental subretinal inflammation in Cx3cr1 deficient mice.
CCR2(+) monocytes infiltrate atrophic lesions in age-related macular disease and mediate photoreceptor degeneration in experimental subretinal inflammation in Cx3cr1 deficient mice.
复制标题
DOI：
10.1002/emmm.201302692
复制
发表时间：
2013-11
影响因子：
11.1
通讯作者：
Combadiere, Christophe
中科院分区：
文献类型：
--
作者：
Sennlaub, Florian;Auvynet, Constance;Calippe, Bertrand;Lavalette, Sophie;Poupel, Lucie;Hu, Shulong J.;Dominguez, Elisa;Camelo, Serge;Levy, Olivier;Guyon, Elodie;Saederup, Noah;Charo, Israel F.;Van Rooijen, Nico;Nandrot, Emeline;Bourges, Jean-Louis;Behar-Cohen, Francine;Sahel, Jose-Alain;Guillonneau, Xavier;Raoul, William;Combadiere, Christophe
萎缩性年龄相关性黄斑变性（AMD）与单核吞噬细胞（MP）的视网膜下积聚有关。它们在促进或抑制视网膜变性中的作用尚不清楚。我们在此发现，萎缩性AMD与患者眼内CCL 2水平升高和视网膜下CCR 2+炎性单核细胞浸润相关。使用年龄和光诱导的视网膜下炎症和光感受器变性Cx 3cr 1基因敲除小鼠，我们表明，视网膜下Cx 3cr 1缺陷的MP过度表达CCL 2和CCL 2或CCR 2的基因缺失和CCR 2的药理学抑制，防止炎症单核细胞募集，MP积累和光感受器变性在体内。我们的研究表明，与CCR 2和CCL 2相反，CX 3CR 1在视网膜中组成型表达，在视网膜中它抑制CCL 2的表达和神经毒性炎性CCR 2+单核细胞的募集。CCL 2/CCR 2抑制可能是控制AMD炎症和神经退行性变的有力工具。
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.
登录
查看更多内容
影响因子：
37.8
作者：
Combadière, C;Potteaux, S;Mallat, Z
通讯作者：
Mallat, Z
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
4.4
作者：
Chen, Mei;Luo, Chang;Xu, Heping
通讯作者：
Xu, Heping
影响因子：
6
作者：
Hisatomi, T;Sakamoto, T;Kroemer, G
通讯作者：
Kroemer, G
影响因子：
56.9
作者：
Edwards, AO;Ritter, R;Farrer, LA
通讯作者：
Farrer, LA