CCR2+ monocytes infiltrate atrophic lesions in age‐related macular disease and mediate photoreceptor degeneration in experimental subretinal inflammation in Cx3cr1 deficient mice
Abstract 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 subr...
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Springer Nature
2013-10-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.1002/emmm.201302692 |
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| author | Florian Sennlaub Constance Auvynet Bertrand Calippe Sophie Lavalette Lucie Poupel Shulong J. Hu Elisa Dominguez Serge Camelo Olivier Levy Elodie Guyon Noah Saederup Israel F. Charo Nico Van Rooijen Emeline Nandrot Jean‐Louis Bourges Francine Behar‐Cohen José‐Alain Sahel Xavier Guillonneau William Raoul Christophe Combadiere |
| author_facet | Florian Sennlaub Constance Auvynet Bertrand Calippe Sophie Lavalette Lucie Poupel Shulong J. Hu Elisa Dominguez Serge Camelo Olivier Levy Elodie Guyon Noah Saederup Israel F. Charo Nico Van Rooijen Emeline Nandrot Jean‐Louis Bourges Francine Behar‐Cohen José‐Alain Sahel Xavier Guillonneau William Raoul Christophe Combadiere |
| author_sort | Florian Sennlaub |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-2ff2d9d1430a4fa785a7b34aa7d9d130 |
| institution | OA Journals |
| issn | 1757-4676 1757-4684 |
| language | English |
| publishDate | 2013-10-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-2ff2d9d1430a4fa785a7b34aa7d9d1302025-08-20T02:18:31ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842013-10-015111775179310.1002/emmm.201302692CCR2+ monocytes infiltrate atrophic lesions in age‐related macular disease and mediate photoreceptor degeneration in experimental subretinal inflammation in Cx3cr1 deficient miceFlorian Sennlaub0Constance Auvynet1Bertrand Calippe2Sophie Lavalette3Lucie Poupel4Shulong J. Hu5Elisa Dominguez6Serge Camelo7Olivier Levy8Elodie Guyon9Noah Saederup10Israel F. Charo11Nico Van Rooijen12Emeline Nandrot13Jean‐Louis Bourges14Francine Behar‐Cohen15José‐Alain Sahel16Xavier Guillonneau17William Raoul18Christophe Combadiere19Inserm, U 968Inserm, U 968Inserm, U 968Inserm, U 968Inserm UMR_S 945, Laboratoire Immunité et InfectionInserm, U 968Inserm, U 968Inserm, U 968Inserm, U 968Inserm, U 968Gladstone Institute of Cardiovascular Disease, San FranciscoGladstone Institute of Cardiovascular Disease, San FranciscoDepartment of Molecular Cell Biology, Free University Medical CenterInserm, U 968Hôtel Dieu, Service d'Ophtalmologie, Centre de Recherche OphtalmologiqueHôtel Dieu, Service d'Ophtalmologie, Centre de Recherche OphtalmologiqueInserm, U 968Inserm, U 968Inserm, U 968Inserm UMR_S 945, Laboratoire Immunité et InfectionAbstract 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.https://doi.org/10.1002/emmm.201302692age‐related macular diseasechemokinesmonocyteneurodegenerationneuroinflammation |
| spellingShingle | Florian Sennlaub Constance Auvynet Bertrand Calippe Sophie Lavalette Lucie Poupel Shulong J. Hu Elisa Dominguez Serge Camelo Olivier Levy Elodie Guyon Noah Saederup Israel F. Charo Nico Van Rooijen Emeline Nandrot Jean‐Louis Bourges Francine Behar‐Cohen José‐Alain Sahel Xavier Guillonneau William Raoul Christophe Combadiere 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 age‐related macular disease chemokines monocyte neurodegeneration neuroinflammation |
| title | CCR2+ monocytes infiltrate atrophic lesions in age‐related macular disease and mediate photoreceptor degeneration in experimental subretinal inflammation in Cx3cr1 deficient mice |
| title_full | CCR2+ monocytes infiltrate atrophic lesions in age‐related macular disease and mediate photoreceptor degeneration in experimental subretinal inflammation in Cx3cr1 deficient mice |
| title_fullStr | CCR2+ monocytes infiltrate atrophic lesions in age‐related macular disease and mediate photoreceptor degeneration in experimental subretinal inflammation in Cx3cr1 deficient mice |
| title_full_unstemmed | CCR2+ monocytes infiltrate atrophic lesions in age‐related macular disease and mediate photoreceptor degeneration in experimental subretinal inflammation in Cx3cr1 deficient mice |
| title_short | CCR2+ monocytes infiltrate atrophic lesions in age‐related macular disease and mediate photoreceptor degeneration in experimental subretinal inflammation in Cx3cr1 deficient mice |
| title_sort | ccr2 monocytes infiltrate atrophic lesions in age related macular disease and mediate photoreceptor degeneration in experimental subretinal inflammation in cx3cr1 deficient mice |
| topic | age‐related macular disease chemokines monocyte neurodegeneration neuroinflammation |
| url | https://doi.org/10.1002/emmm.201302692 |
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