CCR2+ monocytes infiltrate atrophic lesions in age-related macular disease and mediate photoreceptor degeneration in experimental subretinal inflammation in Cx3cr1 deficient mice

被引：236

作者：

Sennlaub, Florian ^{[1
,2
,3
,4
]}

Auvynet, Constance ^{[1
,5
,6
]}

Calippe, Bertrand ^{[1
,2
,3
]}

Lavalette, Sophie ^{[1
,2
,3
]}

Poupel, Lucie ^{[5
,6
]}

Hu, Shulong J. ^{[1
,2
,3
]}

Dominguez, Elisa ^{[1
,2
,3
]}

Camelo, Serge ^{[1
,2
,3
]}

Levy, Olivier ^{[1
,2
,3
]}

Guyon, Elodie ^{[1
,5
,6
]}

Saederup, Noah ^{[7
,8
]}

Charo, Israel F. ^{[7
,8
]}

Van Rooijen, Nico ^{[9
]}

Nandrot, Emeline ^{[1
,2
,3
]}

Bourges, Jean-Louis ^{[4
,10
,11
,12
]}

Behar-Cohen, Francine ^{[4
,10
,11
,12
]}

Sahel, Jose-Alain ^{[1
,2
,3
]}

Guillonneau, Xavier ^{[1
,2
,3
]}

Raoul, William ^{[1
,2
,3
]}

Combadiere, Christophe ^{[5
,6
,13
]}

机构：

[1] INSERM, U 968, Paris, France

[2] Univ Paris 06, UPMC, UMR S 968, Inst Vis, Paris, France

[3] Ctr Hosp Natl Ophtalmol Quinze Vingts, INSERM, DHOS CIC 503, Paris, France

[4] Ctr Rech Ophtalmol, Hotel Dieu, Serv Ophtalmol, Paris, France

[5] Lab Immunite & Infect, INSERM, UMR S 945, Paris, France

[6] Univ Paris 06, UPMC, UMR S 945, Paris, France

[7] Gladstone Inst Cardiovasc Dis, San Francisco, CA USA

[8] Univ Calif San Francisco, Cardiovasc Res Inst, Dept Med, San Francisco, CA 94143 USA

[9] Free Univ Amsterdam, Dept Mol Cell Biol, Med Ctr, Amsterdam, Netherlands

[10] Ctr Rech Cordeliers, INSERM, UMR S 872, Paris, France

[11] Univ Paris 05, Ctr Rech Cordeliers, UMR S 872, Paris, France

[12] Univ Paris 06, UPMC, UMR S 872, Paris, France

[13] Grp Hosp Pitie Salpetriere, AP HP, Serv Immunol, F-75634 Paris, France

来源：

EMBO MOLECULAR MEDICINE | 2013年 / 5卷 / 11期

关键词：

age-related macular disease; chemokines; monocyte; neurodegeneration; neuroinflammation; FACTOR-H POLYMORPHISM; CHEMOATTRACTANT PROTEIN-1; RETINAL DEGENERATION; BONE-MARROW; GEOGRAPHIC ATROPHY; MYELOID CELLS; MICROGLIA; RECEPTOR; EXPRESSION; CHEMOKINE;

D O I：

10.1002/emmm.201302692

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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.

引用

页码：1775 / 1793

页数：19

共 76 条

[1] An animal model of age-related macular degeneration in senescent Ccl-2-or Ccr-2-deficient mice [J].