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CX3CR1-dependent subretinal microglia cell accumulation is associated with cardinal features of age-related macular degeneration
Open accessAbstract
The role of retinal microglial cells (MCs) in age-related macular degeneration (AMD) is unclear. Here we demonstrated that all retinal MCs express CX3C chemokine receptor 1 (CX3CR1) and that homozygosity for the CX3CR1 M280 allele, which is associated with impaired cell migration, increases the risk of AMD. In humans with AMD, MCs accumulated in the subretinal space at sites of retinal degeneration and choroidal neovascularization (CNV). In CX3CR1-deficient mice, MCs accumulated subretinally with age and albino background and after laser impact preceding retinal degeneration. Raising the albino mice in the dark prevented both events. The appearance of lipid-bloated subretinal MCs was drusen-like on funduscopy of senescent mice, and CX3CR1-dependent MC accumulation was associated with an exacerbation of experimental CNV. These results show that CX3CR1-dependent accumulation of subretinal MCs evokes cardinal features of AMD. These findings reveal what we believe to be a novel pathogenic process with important implications for the development of new therapies for AMD.
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In the citing paper
“Cx3cr1 knockout mice exhibited age-dependent subretinal microglial accumulation and retinal degeneration.37,38”
From CX3CR1 Deficiency Alters Microglial Activation and Reduces Beta-Amyloid Deposition in Two Alzheimer's Disease Mouse Models (2010) · cites this paper as [37]
In the citing paper
“In a French study, homozygosity for the CX3CR1 T280M allele was also reported to be associated with AMD (Combadiere et al., 2007).”
From Molecular pathology of age-related macular degeneration (2009) · cites this paper as Combadiere et al., 2007
In the citing paper
“whose immunohistochemical analysis in humans showed that CX3CR1 was expressed on all retinal microglial cells, and these cells are the only cells in the retina that express CX3CR1.”
From Molecular pathology of age-related macular degeneration (2009) · cites this paper as Combadiere et al., 2007
In the citing paper
“Their immunohistochemical analysis of AMD cases suggest that CX3CR1-positive microglial cells accumulated subretinally in affected areas of the macula”
From Molecular pathology of age-related macular degeneration (2009) · cites this paper as Combadiere et al., 2007
In the citing paper
“Moreover, Cx3cr1−/− mice exhibited increased microglial accumulation after laser-injury, as well as worsened laser-induced CNV and retinal degeneration.”
From Molecular pathology of age-related macular degeneration (2009) · cites this paper as Combadiere et al., 2007
In the citing paper
“Cx3cr1−/− mice demonstrated retinal degeneration and drusen-like deposits, which contained bloated accumulated microglia capable of phagocytosing outer segments of photoreceptor cells in 18 months and older mice.”
From Molecular pathology of age-related macular degeneration (2009) · cites this paper as Combadiere et al., 2007
In the citing paper
“The CX3CR1 SNP is associated with impaired microglial chemotaxis (Combadiere et al., 2007).”
From Molecular pathology of age-related macular degeneration (2009) · cites this paper as Combadiere et al., 2007
In the citing paper
“CX3CR1 positive cells in drusen and near CNV membranes are microglial cells in human AMD eyes (Combadiere et al., 2007).”
From Molecular pathology of age-related macular degeneration (2009) · cites this paper as Combadiere et al., 2007
In the citing paper
“Age-related macular degeneration (AMD) is associated with chronic inflammation [29, 65] and altered fecal microbial metabolite profiles [100].”
From Fecal microbiota transfer between young and aged mice reverses hallmarks of the aging gut, eye, and brain (2022) · cites this paper as [29]
In the citing paper
“homozygosity of the M280 allele showed defective cell migration and appeared to be associated with higher AMD susceptibility (30).”
From Unraveling a Multifactorial Late-Onset Disease: From Genetic Susceptibility to Disease Mechanisms for Age-Related Macular Degeneration (2009) · cites this paper as [30]
In the citing paper
“Homozygosity of the CX3CR1 M280 allele and V249I allele, associated with impaired microglial cell migration, has been shown to increase the risk of AMD (Combadiere et al., 2007; Tuo et al., 2004).”
From Retinal ultrastructure of murine models of dry age-related macular degeneration (AMD) (2010) · cites this paper as Combadiere et al., 2007
In the citing paper
“At 12 months of age, ultrastructural analysis of senescent Cx3cr1−/− mice revealed subretinal cells that contained intracellular lipid deposits and outer segment remnants between the photoreceptor outer segment and RPE.”
From Retinal ultrastructure of murine models of dry age-related macular degeneration (AMD) (2010) · cites this paper as Combadiere et al., 2007
In the citing paper
“At this age, the Cx3cr1−/− mice had significant (40%) thinning of the outer retina, mainly the outer nuclear layer, which progressed to marked degeneration of the photoreceptor layer by 4 months of age when compared to wild-type mice.”
From Retinal ultrastructure of murine models of dry age-related macular degeneration (AMD) (2010) · cites this paper as Combadiere et al., 2007
In the citing paper
“At 18 months of age, the engorged subretinal microglial cells appeared drusen-like on fundoscopy (Combadiere et al., 2007).”
From Retinal ultrastructure of murine models of dry age-related macular degeneration (AMD) (2010) · cites this paper as Combadiere et al., 2007
In the citing paper
“After laser injury, Cx3cr1−/− mice showed signs of significant CNV compared to wild-type mice (Combadiere et al., 2007).”
From Retinal ultrastructure of murine models of dry age-related macular degeneration (AMD) (2010) · cites this paper as Combadiere et al., 2007
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Citations
Cites
Blood Monocytes Consist of Two Principal Subsets with Distinct Migratory Properties
Geissmann, F., Jung, S., & Littman, D. R. (2003) · Immunity · doi:10.1016/s1074-7613(03)00174-2 · Cited by 3,504
Prevalence of Age-Related Macular Degeneration in the United States
The Eye Diseases Prevalence Research Group* (2004) · Archives of Ophthalmology · doi:10.1001/archopht.122.4.564 · Cited by 2,774
Jung, S., Aliberti, J., Graemmel, P., Sunshine, M. J., Kreutzberg, G. W., Sher, A., & Littman, D. R. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.11.4106-4114.2000 · Cited by 2,632
Complement factor H polymorphism and age-related macular degeneration
Edwards, A. O., Ritter, R., Abel, K. J., Manning, A., Panhuysen, C., & Farrer, L. A. (2005) · Science · doi:10.1126/science.1110189 · Cited by 2,449
Complement factor H variant increases the risk of age-related macular degeneration
Haines, J. L., Hauser, M. A., Schmidt, S., Scott, W. K., Olson, L. M., Gallins, P., Spencer, K. L., Kwan, S. Y., Noureddine, M., Gilbert, J. R., et al. (2005) · Science · doi:10.1126/science.1110359 · Cited by 2,424
Bird, A. C., Bressler, N. M., Bressler, S. B., Chisholm, I. H., Coscas, G., Davis, M. D., de Jong, P. T. V. M., Klaver, C. C. W., Klein, B. E. K., Klein, R., et al. (1995) · Survey of Ophthalmology · doi:10.1016/s0039-6257(05)80092-x · Cited by 1,926
AN INVESTIGATION OF CORONARY HEART DISEASE IN FAMILIES
Kannel, W. B., Feinleib, M., McNAMARA, P. M., Garrison, R. J., & Castelli, W. P. (1979) · American Journal of Epidemiology · doi:10.1093/oxfordjournals.aje.a112813 · Cited by 1,639
Control of microglial neurotoxicity by the fractalkine receptor
Cardona, A. E., Pioro, E. P., Sasse, M. E., Kostenko, V., Cardona, S. M., Dijkstra, I. M., Huang, D., Kidd, G., Dombrowski, S., Dutta, R., et al. (2006) · Nature Neuroscience · doi:10.1038/nn1715 · Cited by 1,531
Hageman, G. (2001) · Progress in Retinal and Eye Research · doi:10.1016/s1350-9462(01)00010-6 · Cited by 1,265
Mullins, R. F., Russell, S. R., Anderson, D. H., & Hageman, G. S. (2000) · The FASEB Journal · doi:10.1096/fasebj.14.7.835 · Cited by 937
Flagged first, then by citations
Research works printed but not linked: 2
- Ng, 2001, Invest. Ophthalmol. Vis. Sci., 42, 3301
- Matsubara, 1999, Invest. Ophthalmol. Vis. Sci., 40, 3186
Cited by
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Items 201–300 of 624
Telegina, D. V., Kozhevnikova, O. S., Bayborodin, S. I., & Kolosova, N. G. (2017) · Scientific Reports · doi:10.1038/srep41533 · Cited by 57
Comprehensive analysis of mouse retinal mononuclear phagocytes
Lückoff, A., Scholz, R., Sennlaub, F., Xu, H., & Langmann, T. (2017) · Nature Protocols · doi:10.1038/nprot.2017.032 · Cited by 56
Self-citationMicroglia Activation and Inflammation During the Death of Mammalian Photoreceptors
Karlen, S. J., Miller, E. B., & Burns, M. E. (2020) · Annual Review of Vision Science · doi:10.1146/annurev-vision-121219-081730 · Cited by 58
Role of the chemokine receptor CX3CR1 in the mobilization of phagocytic retinal microglial cells
Raoul, W., Keller, N., Rodéro, M., Behar-Cohen, F., Sennlaub, F., & Combadière, C. (2008) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2008.04.014 · Cited by 60
“bright-light model and in our experiments with albino CX3CR1 -/mice (Combadière et al., 2007), together with the observation by Ng et al.”
BackgroundInfluentialSelf-citationThe Role of the Microglial Cx3cr1 Pathway in the Postnatal Maturation of Retinal Photoreceptors
Jobling, A. I., Waugh, M., Vessey, K. A., Phipps, J. A., Trogrlic, L., Greferath, U., Mills, S. A., Tan, Z. L., Ward, M. M., & Fletcher, E. L. (2018) · Journal of Neuroscience · doi:10.1523/jneurosci.2368-17.2018 · Cited by 55
“…a role for the Cx3cr1 signaling pathway in age-related macular degeneration (AMD; Tuo et al., 2004; Chen et al., 2007; Raoul et al., 2010), with the Cx3cr1GFP/GFP mouse model exhibiting fundus lesions and retinal degeneration at 18 months of age (Combadière et al., 2007; Raoul et al., 2008).”
BackgroundResultInfluentialRedefining our vision: an updated guide to the ocular immune system
Wu, M., Fletcher, E. L., Chinnery, H. R., Downie, L. E., & Mueller, S. N. (2024) · Nature reviews. Immunology · doi:10.1038/s41577-024-01064-y · Cited by 60
“In aged mice that are CX 3 CR1-deficient, rod photoreceptors are also reduced in number 143 , highlighting the importance of microglia–photoreceptor communication in both the developing and adult retina.”
Yeo, S.-I., Kim, J.-E., Ryu, H. J., Seo, C. H., Lee, B. C., Choi, I.-G., Kim, D.-S., & Kang, T.-C. (2011) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2011.03.005 · Cited by 55
“In addition, CX3CR1 KO microglia have been shown to accumulate and promote retinal degeneration (Combadière et al., 2007).”
(2011) · Europe PMC (PubMed Central) · Cited by 55
The role of microglia in the progression of glaucomatous neurodegeneration- a review
Zeng, H.-L., & Shi, J. (2018) · International Journal of Ophthalmology · doi:10.18240/ijo.2018.01.22 · Cited by 54
Liu, C., Luo, D., Streit, W. J., & Harrison, J. K. (2008) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2008.04.016 · Cited by 55
“CX3CR1 deficiency results in impaired microglia migration in a mouse model of age-related macular degeneration (Combadiere et al., 2007).”
Sheets, K. G., Jun, B., Zhou, Y., Zhu, M., Petasis, N. A., Gordon, W. C., & Bazan, N. G. (2013) · Europe PMC (PubMed Central) · Cited by 54
γδ T Cells as a Major Source of IL-17 Production During Age-Dependent RPE Degeneration
Zhao, Z., Xu, P., Jie, Z., Zuo, Y., Yu, B., Soong, L., Sun, J., Chen, Y., & Cai, J. (2014) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.14-15166 · Cited by 54
RAGE Regulates Immune Cell Infiltration and Angiogenesis in Choroidal Neovascularization
Chen, M., Glenn, J. V., Dasari, S., McVicar, C., Ward, M. S., Colhoun, L. M., Quinn, M. P., Bierhaus, A., Xu, H., & Stitt, A. W. (2014) · PLoS ONE · doi:10.1371/journal.pone.0089548 · Cited by 54
“Indeed, activation of resident microglia and infiltration of immune cells into the subretinal space are important aspects of the laser-induced CNV response in mice [48,49] and it has been suggested that these cells may be a driving force in the pathogenesis of AMD and not simply a secondary consequence of primary RPE…”
BackgroundThe role of lymphocytes and phagocytes in age-related macular degeneration (AMD)
Behnke, V., Wolf, A., & Langmann, T. (2020) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03419-4 · Cited by 55
Economopoulou, M., Hammer, J. A., Wang, F., Fariss, R. N., Maminishkis, A., & Miller, S. S. (2009) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.08-2129 · Cited by 54
Aredo, B., Zhang, K., Chen, X., Wang, C. X.-Z., Li, T., & Ufret-Vincenty, R. L. (2015) · Journal of Neuroinflammation · doi:10.1186/s12974-014-0221-4 · Cited by 53
Models of retinal diseases and their applicability in drug discovery
Malek, G., Busik, J. V., Grant, M. B., & Choudhary, M. (2018) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2018.1430136 · Cited by 53
In Vivo Laser-Mediated Retinal Ganglion Cell Optoporation Using KV1.1 Conjugated Gold Nanoparticles
Wilson, A. M., Mazzaferri, J., Bergeron, É., Patskovsky, S., Marcoux-Valiquette, P., Costantino, S., Sapieha, P. S., & Michel Meunier, A. (2018) · Nano Letters · doi:10.1021/acs.nanolett.8b02896 · Cited by 53
Melanophages give rise to hyperreflective foci in AMD, a disease-progression marker
Augustin, S., Lam, M., Lavalette, S., Verschueren, A., Blond, F., Forster, V., Przegralek, L., He, Z., Lewandowski, D., Bemelmans, A., et al. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02699-9 · Cited by 52
“As MPs have been shown to infiltrate the diseased retina in intermediate and late AMD [3, 12, 15, 16, 27], these results strongly suggest that the majority of HRF in AMD are caused by pigment-laden MPs called melanophages that have been well described in skin diseases [20–22].”
BackgroundResultSelf-citationFunctional Adhesiveness of the CX3CL1 Chemokine Requires Its Aggregation
Hermand, P., Pincet, F., Carvalho, S., Ansanay, H., Trinquet, E., Daoudi, M., Combadière, C., & Déterre, P. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m802638200 · Cited by 56
Self-citationCX3CR1 deficiency accelerates the development of retinopathy in a rodent model of type 1 diabetes
Beli, E., Dominguez, J. M., Hu, P., Thinschmidt, J. S., Caballero, S., Calzi, S. L., Luo, D., Shanmugam, S., Salazar, T. E., Duan, Y., et al. (2016) · Journal of Molecular Medicine · doi:10.1007/s00109-016-1433-0 · Cited by 52
“Finally, other studies have shown that even under normal conditions CX3CR1-deficient mice exhibit accumulation of subretinal microglia and macrophages [42,43,25].”
The Effects of Age and Cx 3 cr1 Deficiency on Retinal Microglia in the Ins2 Akita Diabetic Mouse
Kezic, J. M., Chen, X., Rakoczy, E. P., & McMenamin, P. G. (2013) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.12-10876 · Cited by 53
Ccl2/Cx3cr1 Knockout Mice Have Inner Retinal Dysfunction but Are Not an Accelerated Model of AMD
Vessey, K. A., Greferath, U., Jobling, A. I., Phipps, J. A., Ho, T., Waugh, M., & Fletcher, E. L. (2012) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.12-10650 · Cited by 51
Age-related macular degeneration: genetic and clinical findings
Kokotas, H., Grigoriadou, M., & Petersen, M. B. (2010) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm.2011.091 · Cited by 55
“They also found that chemotaxis of monocytes from individuals with homozygous I249/M280 genotypes was impaired in the presence of bound CX3CR1 (110).”
BackgroundInfluentialMTOR‐initiated metabolic switch and degeneration in the retinal pigment epithelium
Go, Y., Zhang, J., Fernandes, J., Litwin, C., Chen, R., Wensel, T. G., Jones, D. P., Cai, J., & Chen, Y. (2020) · The FASEB Journal · doi:10.1096/fj.202000612r · Cited by 52
Luhmann, U. F. O., Carvalho, L. S., Robbie, S. J., Cowing, J. A., Durán, Y., Munro, P., Bainbridge, J. W., & Ali, R. R. (2012) · Experimental Eye Research · doi:10.1016/j.exer.2012.11.015 · Cited by 51
“…on subretinal microglia accumulation and retinal degeneration has already been described in different chemokine lines (Chinnery et al., 2012; Combadiere et al., 2007), but has in particular been highlighted in a model of light-induced retinal damage where healthy C57Bl/6J-Tyrc2j mice, which…”
BackgroundInfluentialMathis, T., Housset, M., Eandi, C. M., Béguier, F., Touhami, S., Reichman, S., Augustin, S., Gondouin, P., Sahel, J., Kodjikian, L., et al. (2016) · Aging Cell · doi:10.1111/acel.12540 · Cited by 50
“…immunosuppressive factors, such as Fas ligand (FasL), that lead to a quick elimination of leukocytes (Griffith et al., 1995; Levy et al., 2015a) and participates in keeping the subretinal space physiologically devoid of immune cells (Gupta et al., 2003; Combadi ere et al., 2007; Lad et al., 2015).”
BackgroundMethodInfluentialSelf-citationMurinello, S., Mullins, R. F., Lotery, A. J., Perry, V. H., & Teeling, J. L. (2014) · Investigative Opthalmology & Visual Science · doi:10.1167/iovs.13-11821 · Cited by 51
Hu, M. L., Quinn, J., & Xue, K. (2021) · Life · doi:10.3390/life11070635 · Cited by 51
“The previously mentioned TRE2 mice carrying human APOE2 demonstrate the accumulation of sub-RPE debris and subretinal mononuclear phagocytes with age [45,108].”
BackgroundFractalkine/CX3CR1-Dependent Modulation of Synaptic and Network Plasticity in Health and Disease
Camacho-Hernández, N. P., & Peña‐Ortega, F. (2023) · Neural Plasticity · doi:10.1155/2023/4637073 · Cited by 52
“In the diabetic retina, there is an exacerbated subretinal microglial accumulation in CX3CR1 mice compared to wild-type animals [161, 163].”
BackgroundThrombospondin-1-mediated regulation of microglia activation after retinal injury
Ng, T. F., Turpie, B., & Masli, S. (2009) · Investigative Opthalmology & Visual Science · doi:10.1167/iovs.08-2877 · Cited by 48
Landowski, M., & Rickman, C. B. (2021) · Journal of Ocular Pharmacology and Therapeutics · doi:10.1089/jop.2021.0067 · Cited by 48
Ardeljan, C., Ardeljan, D., Abu-Asab, M. S., & Chan, C. (2014) · Journal of Clinical Medicine · doi:10.3390/jcm3041542 · Cited by 53
“mice showed subretinal microglial accumulation and retinal degeneration associated with aging, laser injury, and albinism; additionally, microglial cells adjacent to the site of laserinduced CNV expressed VEGF, indicating that they may contribute to the initiation, maintenance, and progression of CNV [29].”
BackgroundInfluentialFletcher, E. L. (2020) · Ophthalmic and Physiological Optics · doi:10.1111/opo.12671 · Cited by 49
“One of the more prominent features that occurs in retinae with age is the accumulation of cells of the innate immune system within the subretinal space.(25,40,47,48) As shown in Figure 2, immune cells accumulate around some of the lesions associated with AMD, especially reticular pseudodrusen, and have also been repor…”
BackgroundKezic, J. M., Xu, H., Chinnery, H. R., Murphy, C. C., & McMenamin, P. G. (2008) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.07-0953 · Cited by 48
“Since submission of this manuscript, a very detailed analysis of this phenomenon has been published that suggests a possible dysfunction in the retinas of aged transgenic albino mice that lack Cx3cr1.”
BackgroundInfluentialJin, N., Gao, L., Fan, X., & Xu, H. (2016) · Molecular Neurobiology · doi:10.1007/s12035-016-9960-9 · Cited by 47
Hu, H., Liu, Y., Wang, L., & Li, W. (2017) · PLoS ONE · doi:10.1371/journal.pone.0173716 · Cited by 47
A Review of the Role of the Intestinal Microbiota in Age-Related Macular Degeneration
Lin, P., McClintic, S. M., Nadeem, U., & Skondra, D. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10102072 · Cited by 48
Borchert, G. A., Shamsnajafabadi, H., Hu, M. L., Silva, S. R. D., Downes, S. M., MacLaren, R. E., Xue, K., & Cehajic‐Kapetanovic, J. (2023) · Cells · doi:10.3390/cells12162092 · Cited by 53
CX3CL1 (Fractalkine) Protein Expression in Normal and Degenerating Mouse Retina: In Vivo Studies
Zieger, M. V., Ahnelt, P. K., & Uhrín, P. (2014) · PLoS ONE · doi:10.1371/journal.pone.0106562 · Cited by 46
Angiogenesis in eye disease: immunity gained or immunity lost?
Ferguson, T. A., & Apte, R. S. (2008) · Seminars in Immunopathology · doi:10.1007/s00281-008-0113-8 · Cited by 46
“Further, we propose that resident macrophages (e.g., resident retinal microglial cells) from aged individuals who develop neovascular AMD have shifted their functional type from anti-angiogenic M1 to pro-angiogenic M2. Indeed, a defect in phagocytic clearing of debris is supported by recent observations in the mouse s…”
BackgroundExperimental Models in Neovascular Age Related Macular Degeneration
Rastoin, O., Pagès, G., & Dufies, M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21134627 · Cited by 52
“This knockout model has been widely thought to induce drusen, thickening of Bruch’s membrane, photoreceptor malfunction, and occurrence of CNV [45].”
BackgroundInfluentialHuang, K., Liu, X., Lv, Z., Zhang, D., Zhou, Y., Lin, Z., & Guo, J. (2023) · Small · doi:10.1002/smll.202207335 · Cited by 44
Eye on the horizon: The metabolic landscape of the RPE in aging and disease
Hansman, D., Du, J., Casson, R. J., & Peet, D. J. (2024) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2024.101306 · Cited by 50
In vivo observation of the locomotion of microglial cells in the retina
Pâques, M., Simonutti, M., Augustin, S., Goupille, O., Mathari, B. E., & Sahel, J. (2010) · Glia · doi:10.1002/glia.21037 · Cited by 44
Knockout of Ccr2 alleviates photoreceptor cell death in rodent retina exposed to chronic blue light
Hu, Z., Zhang, Y., Wang, J., Mao, P., Lv, X., Yuan, S., Huang, Z., Ding, Y., Xie, P., & Liu, Q. (2016) · Cell Death and Disease · doi:10.1038/cddis.2016.363 · Cited by 45
“In AMD patients, microglia are activated and accumulate in the subretinal space.(23,24) Of note, microglia”
BackgroundZhang, Y., Wang, X., Sadda, S. R., Clark, M. E., Witherspoon, C. D., Spaide, R. F., Owsley, C. J., & Curcio, C. A. (2019) · Ophthalmology Retina · doi:10.1016/j.oret.2019.10.012 · Cited by 44
Retinal microglia are critical for subretinal neovascular formation
Usui‐Ouchi, A., Usui, Y., Kurihara, T., Aguilar, E., Dorrell, M. I., Ideguchi, Y., Sakimoto, S., Bravo, S., & Friedlander, M. (2020) · JCI Insight · doi:10.1172/jci.insight.137317 · Cited by 44
“It was also reported that retinal microglia accumulated in affected zones of the maculae of patients with AMD and located in close physical contact with choroidal NV (33).”
BackgroundZinkernagel, M. S., Chinnery, H. R., Ong, M. L., Petitjean, C., Voigt, V., McLenachan, S., McMenamin, P. G., Hill, G. R., Forrester, J. V., Wikström, M. E., et al. (2013) · American Journal Of Pathology · doi:10.1016/j.ajpath.2012.11.031 · Cited by 44
Qin, S., & Rodrigues, G. A. (2008) · Journal of Inflammation Research · doi:10.2147/jir.s4354 · Cited by 43
“These knockout mice display many of the features of AMD including the accumulation of lipofuscin, A2E, drusen as well as photoreceptor atrophy and CNV. Additionally, in the case of the CX3CR1 knockouts, subretinal accumulation of microglial cells was observed (Combadiere et al 2007; Tuo et al 2007).”
InfluentialDhingra, A., Bell, B. A., Peachey, N. S., Daniele, L. L., Reyes-Reveles, J., Sharp, R. C., Jun, B., Bazan, N. G., Sparrow, J. R., Kim, H. J., et al. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00351 · Cited by 41
“RPE cultures derived from human donor eyes (patients with AMD), exhibited increased intracellular lipid accumulation and oxidative stress.”
BackgroundInfluentialRole of chemokines polymorphisms in diseases
Guergnon, J., & Combadière, C. (2012) · Immunology Letters · doi:10.1016/j.imlet.2012.04.010 · Cited by 42
Self-citationAge- and Light-Dependent Development of Localised Retinal Atrophy in CCL2−/−CX3CR1GFP/GFP Mice
Chen, M., Hombrebueno, J. R., Luo, C., Peñalva, R. G., Zhao, J., Colhoun, L. M., Pandi, S. P. S., Forrester, J. V., & Xu, H. (2013) · PLoS ONE · doi:10.1371/journal.pone.0061381 · Cited by 44
“Although AMD patients do not have CCL2 and CX3CR1 deficiency, many of them do have other immunerelated gene polymorphisms, including genes involved in the complement system [53], TLRs [15,54], and CX3CR1 [16,17,19].”
BackgroundCouturier, A., Bousquet, E., Zhao, M., Naud, M., Klein, C., Jonet, L., Tadayoni, R., de Kozak, Y., & Béhar‐Cohen, F. (2014) · PubMed Central · Cited by 42
Self-citationInflammation in Age-Related Macular Degeneration
Ozaki, E., Campbell, M., Kiang, A., Humphries, M. M., Doyle, S., & Humphries, P. (2014) · Advances in experimental medicine and biology · doi:10.1007/978-1-4614-3209-8_30 · Cited by 41
Interaction of Complement Factor H and Fibulin3 in Age-Related Macular Degeneration
Wyatt, M. K., Tsai, J.-Y., Mishra, S., Campos, M. M., Jaworski, C. J., Fariss, R. N., Bernstein, S. L., & Wistow, G. J. (2013) · PLoS ONE · doi:10.1371/journal.pone.0068088 · Cited by 42
“Associations with several other factors, including complement factors B, C2 [25], C3 [26] and D, and others such as the chemokine receptor CX3CR1 [27], have supported a general inflammatory connection to AMD, although a growing number of other genes have also been linked to the disease, suggesting a degree of heteroge…”
BackgroundApolipoprotein A-I Mimetic Peptide L-4F Removes Bruch's Membrane Lipids in Aged Nonhuman Primates
Rudolf, M., Curcio, C. A., Schlötzer-Schrehardt, U. M., Sefat, A. M. M., Tura, A., Aherrahrou, Z., Brinkmann, M. P., Grisanti, S., Miura, Y., & Ranjbar, M. (2019) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.18-25786 · Cited by 41
Aredo, B., Li, T., Chen, X., Zhang, K., Wang, C. X.-Z., Gou, D., Zhao, B., He, Y.-G., & Ufret-Vincenty, R. L. (2015) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.14-16089 · Cited by 41
“Of particular interest, given the location of the MG/MU in our study, Combadiere et al.(92) and Gupta et al.”
BackgroundEffect of Inhibition of Colony-Stimulating Factor 1 Receptor on Choroidal Neovascularization in Mice
Schwarzer, P., Kokona, D., Ebneter, A., & Zinkernagel, M. S. (2019) · American Journal Of Pathology · doi:10.1016/j.ajpath.2019.10.011 · Cited by 40
Targeting Neurovascular Interaction in Retinal Disorders
Fu, Z., Sun, Y., Cakir, B., Tomita, Y., Huang, S., Wang, Z., Liu, C., Cho, S. S., Britton, W. R., Kern, T. S., et al. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21041503 · Cited by 43
Singh, A., Falk, M. K., Hviid, T. V. F., & Sørensen, T. L. (2013) · Ophthalmology · doi:10.1016/j.ophtha.2012.11.002 · Cited by 40
Zhao, L., Ma, W., Fariss, R. N., & Wong, W. T. (2009) · Experimental Eye Research · doi:10.1016/j.exer.2008.12.013 · Cited by 39
“, 2008), while in another study, the same CX3CR1-deficiency conversely resulted in greater subretinal microglial accumulation and more choroidal neovascularization in response to laserinduced injury (Combadiere et al., 2007).”
BackgroundResultInfluentialHuang, L., Xu, W., & Xu, G. (2013) · Ocular Immunology and Inflammation · doi:10.3109/09273948.2013.791925 · Cited by 40
Update on clinical trials in dry Age-related macular degeneration
Schatz, P., Taşkintuna, İ., & Elsayed, M. E. A. A. (2016) · Middle East African Journal of Ophthalmology · doi:10.4103/0974-9233.173134 · Cited by 40
Loss of Zebrafish Mfrp Causes Nanophthalmia, Hyperopia, and Accumulation of Subretinal Macrophages
Collery, R. F., Volberding, P. J., Bostrom, J. R., Link, B. A., & Besharse, J. C. (2016) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.16-19593 · Cited by 39
Subhi, Y., Nielsen, M. K., Molbech, C. R., & Sørensen, T. L. (2018) · Clinical and Experimental Ophthalmology · doi:10.1111/ceo.13152 · Cited by 38
Touhami, S., Béguier, F., Augustin, S., Charles‐Messance, H., Vignaud, L., Nandrot, E. F., Reichman, S., Forster, V., Mathis, T., Sahel, J., et al. (2018) · Journal of Neuroinflammation · doi:10.1186/s12974-018-1106-8 · Cited by 39
Self-citationLate Outgrowth Endothelial Progenitor Cells in Patients with Age-Related Macular Degeneration
Thill, M., Strunnikova, N. V., Berna, M. J., Gordiyenko, N. V., Schmid, K. M., Cousins, S. W., Thompson, D. J. S., & Csaky, K. G. (2008) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.07-0955 · Cited by 38
New neovascular age‐related macular degeneration is associated with systemic leucocyte activity
Subhi, Y., & Sørensen, T. L. (2016) · Acta Ophthalmologica · doi:10.1111/aos.13330 · Cited by 38
Crespo‐Garcia, S., Reichhart, N., Hernandez-Matas, C., Zabulis, X., Kociok, N., Brockmann, C., Joussen, A. M., & Strauß, O. (2015) · Experimental Eye Research · doi:10.1016/j.exer.2015.07.012 · Cited by 37
“Analyzing the choroid ex vivo, we tracked mononuclear phagocytes using Iba-1, detecting their migration out of the neural retina (Combadiere et al., 2007), showing similar behavior in both laser treatments.”
MethodRole of CX3CR1 Receptor in Monocyte/Macrophage Driven Neovascularization
Kumar, A. H. S., Martin, K., Turner, E. C., Büneker, C. K., Dorgham, K., Déterre, P., & Caplice, N. M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0057230 · Cited by 35
“phages are proposed to participate in angiogenesis [1,4,20,21,22]”
BackgroundJensen, E. G., Jakobsen, T. S., Thiel, S., Askou, A. L., & Corydon, T. J. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21249752 · Cited by 40
“Furthermore, microglia were found to be recruited to the outer retina and secrete C3 [119], and, in wAMD patients, microglia have been found in close contact with the CNV-complex [123] (Figure 4C).”
BackgroundDeficiency in the metabolite receptor SUCNR1 (GPR91) leads to outer retinal lesions
Favret, S., Binet, F., Lapalme, E., Leboeuf, D., Carbadillo, J., Rubic, T., Picard, É., Mawambo, G., Tetreault, N., Joyal, J., et al. (2013) · Aging · doi:10.18632/aging.100563 · Cited by 37
“Moreover, resident microglia amass in the subretinal space of CX3CR1-deficient mice at sites of drusen formation and retinal degeneration [18].”
InfluentialSelf-citationCorrection: Choroid Sprouting Assay: An Ex Vivo Model of Microvascular Angiogenesis
Shao, Z., Friedlander, M. S. H., Hurst, C. G., Cui, Z., Pei, D. T., Evans, L. P., Juan, A. M., Tahiri, H., Duhamel, F., Chen, J., et al. (2013) · PLoS ONE · doi:10.1371/annotation/c6b85ec4-996d-4daf-863a-44260a888470 · Cited by 37
Self-citationMcCarthy, C. A., Widdop, R. E., Deliyanti, D., & Wilkinson‐Berka, J. L. (2013) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/1440-1681.12099 · Cited by 36
“and MCP-1 showing the accumulation of microglia and drusen in the subretinal space, degeneration of the RPE, choroidal neovascularization and atrophy of photoreceptors.(30,31) Diabetic retinopathy is the major cause of vision impairment and loss in people of working age.”
BackgroundChemokine receptors as important regulators of pathogenesis during arboviral encephalitis
Michlmayr, D., & Lim, J. K. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00264 · Cited by 38
“Since these cells exclusively express CX3CR1 in the healthy CNS, and its ligand CX3CL1 is constitutively expressed by neurons, this receptor:ligand interaction is likely to function during infection (Harrison et al., 1998; Cardona et al., 2006; Combadiere et al., 2007).”
BackgroundProvost, A. C., Vede, L., Bigot, K., Keller, N., Tailleux, A., ̈s, J.-P. J., Savoldelli, M., Ameqrane, I., Lacassagne, E., Legeais, J., et al. (2009) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.08-2527 · Cited by 36
“We also investigated whether the possible deleterious lesions that may be triggered by such a treatment over a long period share similarities with known features of some forms of human AMD.”
BackgroundInfluentialSelf-citationJobling, A. I., Vessey, K. A., Waugh, M., Mills, S. A., & Fletcher, E. L. (2013) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.13-11831 · Cited by 35
Desforges, N. M., Hebron, M. L., Algarzae, N. K., Lonskaya, I., & Moussa, C. (2012) · International Journal of Alzheimer s Disease · doi:10.1155/2012/345472 · Cited by 36
Hata, M., Hata, M., Andriessen, E. M. M. A., Juneau, R., Pilon, F., Crespo‐Garcia, S., Diaz-Marin, R., Guber, V., Binet, F., Fournier, F., et al. (2023) · Journal of Clinical Investigation · doi:10.1172/jci159757 · Cited by 35
“Activated phagocytes are found in the subretinal space of AMD patients (18).”
BackgroundLenin, R. R., Koh, Y., Zhang, Z., Yeo, Y., Parikh, B. H., Seah, I. Y. J., Wong, W., & Su, X. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24108763 · Cited by 33
Dabouz, R., Cheng, C. W. H., Abram, P., Omri, S., Cagnone, G., Sawmy, K. V., Joyal, J., Desjarlais, M., Olson, D. M., Weil, A. G., et al. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-02032-8 · Cited by 34
Self-citationZhao, J., Chen, M., & Xu, H. (2014) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.14-15495 · Cited by 36
The homozygous CX3CR1-M280 mutation impairs human monocyte survival
Collar, A. L., Swamydas, M., O’Hayre, M., Sajib, M. S., Hoffman, K. W., Singh, S. P., Mourad, A., Johnson, M. D., Ferré, E. M. N., Farber, J. M., et al. (2018) · JCI Insight · doi:10.1172/jci.insight.95417 · Cited by 34
“At the population genetic level, the CX3CR1-M280 mutation has thus far been shown to modulate the risk for development of cardiovascular disease, the leading cause of death in the US (17, 19, 20, 36); age-related macular degeneration, a leading cause of blindness in adults > 50 years old in the US (18); systemic candi…”
BackgroundCX3CL1/CX3CR1 and CCL2/CCR2 Chemokine/Chemokine Receptor Complex in Patients with AMD
Falk, M. K., Singh, A., Faber, C., Nissen, M. H., Hviid, T. V. F., & Sørensen, T. L. (2014) · PLoS ONE · doi:10.1371/journal.pone.0112473 · Cited by 34
“[7, 30] In CX3CR1 knock-out mice microglia cells accumulate in the subretinal space with age after laser injury.”
BackgroundImmune Cells in Subretinal Wound Healing and Fibrosis
Szczepan, M., Llorián‐Salvador, M., Chen, M., & Xu, H. (2022) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2022.916719 · Cited by 34
Chen, M., Luo, C., Peñalva, R. G., & Xu, H. (2013) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.12-10888 · Cited by 33
CCR3 Is Associated with the Death of a Photoreceptor Cell-line Induced by Light Exposure
Kuse, Y., Tsuruma, K., Kanno, Y., Shimazawa, M., & Hara, H. (2017) · Frontiers in Pharmacology · doi:10.3389/fphar.2017.00207 · Cited by 32
“…apolipoprotein E (Souied et al., 1998; Levy et al., 2015), superoxide dismutase (Kimura et al., 2000), complement factor H (Edwards et al., 2005; Haines et al., 2005), and CX3C chemokine receptor 1 (CX3CR1) (Tuo et al., 2004; Combadière et al., 2007) are key factors in the development of dry AMD.”
BackgroundMonickaraj, F., Oruganti, S. R., McGuire, P. G., & Das, A. (2020) · Graefe s Archive for Clinical and Experimental Ophthalmology · doi:10.1007/s00417-020-04884-5 · Cited by 32
Dagkalis, A., Wallace, C. A., Hing, B. W. Q., Liversidge, J., & Crane, I. J. (2009) · Immunology · doi:10.1111/j.1365-2567.2009.03046.x · Cited by 32
Lederman, M., Weiss, A. T., & Chowers, I. (2010) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.08-3019 · Cited by 32
Brandli, A. A., Vessey, K. A., & Fletcher, E. L. (2024) · Journal of Neuroinflammation · doi:10.1186/s12974-024-03055-1 · Cited by 33
Update on the role of genetics in the onset of age-related macular degeneration
Francis, P. J. (2011) · Clinical ophthalmology · doi:10.2147/opth.s11627 · Cited by 32
“Associations in the genes APOE (apolipoprotein E), 53–55 ABCA4 (ATP-binding cassette A4), 56,57 CX3CR1 (chemokine 3 receptor 1), 58,59 PON1, 60 TLR4 (toll-like receptor 4), 61 ERCC6, 62 ELOVL4, 63,64 VLDLR (very low density lipoprotein receptor), 65 fibulin-5, 66 hemicentin-1, 29 TLR3 (toll-like…”
Shen, D., Cao, X., Zhao, L., Tuo, J., Wong, W. T., & Chan, C. (2011) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.10-6114 · Cited by 31
Zhou, Y., Sheets, K. G., Knott, E. J., Regan, C. E., Tuo, J., Chan, C., Gordon, W. C., & Bazan, N. G. (2011) · Experimental Eye Research · doi:10.1016/j.exer.2011.07.017 · Cited by 31
“…of microglia within the lesions of Ccl2−/−/ Cx3cr1−/− mice was previously reported (Ross et al., 2008; Tuo et al., 2007), and light was demonstrated to be a key triggering event in the microglial accumulation-associated retinal degeneration of Cx3cr1-deficient mice (Combadiere et al., 2007).”
BackgroundYuan, Z., Chen, X., Yang, W., Lou, B., Ye, N., & Liu, Y. (2019) · PubMed Central · Cited by 31
The role of oxidized phospholipids in the development of disease
Nie, J. S., Yang, J., Wei, Y., & Wei, X. (2020) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2020.100909 · Cited by 33
Microglia–Neutrophil Interactions Drive Dry AMD-like Pathology in a Mouse Model
Boyce, M., Xin, Y., Chowdhury, O., Shang, P., Liu, H., Koontz, V., Strizhakova, A., Nemani, M., Hose, S., Zigler, J. S., et al. (2022) · Cells · doi:10.3390/cells11223535 · Cited by 31
“Activated microglia are known to induce retinal degeneration in AMD as well as other neurodegenerative diseases [2,3,11,12,15,18,34].”
BackgroundInfluentialPPAR‐γ, Microglial Cells, and Ocular Inflammation: New Venues for Potential Therapeutic Approaches
Malchiodi‐Albedi, F., Matteucci, A., Bernardo, A., & Minghetti, L. (2008) · PPAR Research · doi:10.1155/2008/295784 · Cited by 31
Genetic factors associated with the development of age-related macular degeneration
Sergejeva, O., Botov, R., Liutkevičienė, R., & Kriaučiūnienė, L. (2016) · Medicina · doi:10.1016/j.medici.2016.02.004 · Cited by 31
Metadata
- Authors
- Combadière, C., Feumi, C., Raoul, W., Keller, N., Rodéro, M., Pézard, A., Lavalette, S., Houssier, M., Jonet, L., Picard, E., Debré, P., Sirinyan, M., Deterre, P., Ferroukhi, T., Cohen, S.-Y., Chauvaud, D., Jeanny, J.-C., Chemtob, S., Behar-Cohen, F., & Sennlaub, F.
- Affiliations
- Inserm (FR)
- Centre de Recherche des Cordeliers (FR)
- Centre Hospitalier Universitaire Sainte-Justine (CA)
- Assistance Publique – Hôpitaux de Paris (FR)
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2007-10-01
- Volume
- 117
- Issue
- 10
- Pages
- 2920-2928
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC1994614
- OpenAlex
- W2122311980
- Cited by
- 618
- References
- 48
- Citations by year
- 2026: 14 · 2025: 28 · 2024: 37 · 2023: 28 · 2022: 39 · 2021: 45 · 2020: 38 · 2019: 25 · 2018: 39 · 2017: 22 · 2016: 32 · 2015: 45 · 2014: 29 · 2013: 45 · 2012: 36
- FWCI
- 27.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- HAL (submittedVersion, other-oa)
- HAL (submittedVersion, cc-by-nc-sa)
- Funders
- Agence Nationale de la Recherche
- Institut National de la Santé et de la Recherche Médicale
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Ophthalmology › Retinal Development and Disorders
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Retinal Imaging and Analysis
- Keywords
- age-related macular degeneration, retinal microglia, CX3CR1, choroidal neovascularization, drusen, microglial migration, retinal degeneration, microglial senescence, dark rearing
- MeSH terms
- CX3C Chemokine Receptor 1, Alleles, Animals, Cell Movement, Homozygote, Humans, Macular Degeneration, Male, Polymorphism, Genetic, Retina, Retinal Drusen, Microglia, Mice, Knockout, Receptors, Chemokine, Choroidal Neovascularization, Mice
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