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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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“Microglial cells activated by retinal injury transform into microglial foam cells, and migrate to the injured outer retina (Combadiere et al., 2007), where they participate in the phagocytosis of debris (Egensperger et al., 1996).”
Adamus, G. (2017) · Autoimmunity Reviews · doi:10.1016/j.autrev.2017.01.005 · Cited by 28
“The mice deficient in CCL2 or CCR2 and later double-knockout mice (Ccl2−/−/Cx3cr1−/−) have developed AMD-like retinal lesions and they have been used to study the role chemokines in pathogenicity of AMD [47-49].”
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CCR2/CCL2-mediated inflammation protects photoreceptor cells from amyloid-β-induced apoptosis
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Self-citationKezic, J. M., & McMenamin, P. G. (2010) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.10-5325 · Cited by 28
“More recently, the importance of interactions between the chemokine CX3CL1 and its cognate sole receptor, CX3CR1, has been demonstrated in numerous ocular inflammatory conditions, including experimental autoimmune anterior uveitis(31) and putative murine models of age-related macular degeneration.(32,51) The generatio…”
BackgroundLei, L., Tzekov, R. T., Tang, S., & Kaushal, S. (2012) · PubMed Central · Cited by 28
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“It has been shown that microglia also accumulate in the subretinal space in patients with AMD, and the presence of these microglia coincides with the death of photoreceptors.(9,10) In vitro studies on the interaction of macrophages and RPE support the role of macrophages in RPE cell degeneration, with one study showin…”
BackgroundAAV5-mediated sFLT01 gene therapy arrests retinal lesions in Ccl2−/−/Cx3cr1−/− mice
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“We and others have reported that microglial activation is involved in the formation of retinal lesions in several animal AMD models (Combadiere et al., 2007; Ross et al., 2008).”
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Hyalocyte functions and immunology
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“In AMD, microglia cells, which usually reside in the inner retinal layers, have been reported to migrate to the subretinal space, assuming an activated phenotype, and have been associated with the development of drusen (Combadi ere et al. 2007; Raoul et al. 2008).”
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“…of microglia in diverse models of neurological disorders, such as neuropathic pain (Sun et al., 2007), age-related macular degeneration (Combadière et al., 2007), peripheral lipopolysaccharide injection-induced intracranial inflammation, Parkinson’s disease and amyotrophic lateral…”
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“…activated amoeboid microglia infiltrate the ONL and subretinal space in the degenerating outer retina, where they are associated with neovascular structures (Combadiere et al. 2007), and appear to have a role in the phagocytosis of photoreceptor debris (Gupta et al. 2003; Combadiere et al. 2007).”
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“However, CX3CR1 deficiency has been associated with eye-related disorders [58 – 60]; thus, we do not know the functional consequences of inhibiting seizure-induced retinal immune response with CX3CR1 Ab.”
BackgroundTahiri, H., Omri, S., Yang, C., Duhamel, F., Samarani, S., Ahmad, A., Vézina, M., Bussières, M., Vaucher, E., Sapieha, P. S., et al. (2016) · Scientific Reports · doi:10.1038/srep37391 · Cited by 22
“In mouse models of AMD, macrophages and microglia (tissue-resident macrophages), recruited to the subretinal space, play a crucial role in choroidal blood vessel growth 10,11 .”
Self-citationLennikov, A., Saddala, M. S., Mukwaya, A., Tang, S., & Hu, H. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01903 · Cited by 22
“, cfh mice, C3a, and C5a receptor mice) (9), chemokine (Ccl2 and Ccr2 mice) (10), and oxidative stress (Sod1 mice) (11)— among others—do not accurately mimic the pathophysiology of this disease (12).”
BackgroundQi, X., Pay, S. L., Yan, Y., Thomas, J., Lewin, A. S., Chang, L.-J., Grant, M. B., & Boulton, M. E. (2017) · Molecular Therapy · doi:10.1016/j.ymthe.2017.01.015 · Cited by 22
“A second feature of AMD is the appearance of activated microglia in the subretinal space.(28,29) Here, we show in retinal flat mounts a significant numbers of Iba1 microglia 6 months after Sod2 knockdown, and these Iba1 cells exhibited morphological characteristics of ramified and activated microglia (Figure 6C).”
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Retinal phagocytes in age-related macular degeneration
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“CX3CR1 regulates microglia colonization and distribution in the brain [69], and Cx3cr1 gene-deleted mice exhibited lower microglial density in the developing brain [70].”
BackgroundChen, X., Kezic, J. M., Forrester, J. V., Goldberg, G. L., Wicks, I. P., Bernard, C. C. A., & McMenamin, P. G. (2015) · Journal of Neuroinflammation · doi:10.1186/s12974-015-0235-6 · Cited by 22
“C57Bl/6 J Cx3cr1 GFP/+ mice [12] have been widely used to investigate the role of microglia in numerous ocular conditions that may have an inflammatory element in their pathogenesis including potential models of retinal degeneration [65], retinopathy of prematurity [66,67] and diabetic retinopathy [16].”
BackgroundHo, T., Lo, H., Liu, I.-C., Lin, K.-A., Liao, Y., Lo, Y.-C., & Hsiang, C. (2020) · Food & Function · doi:10.1039/d0fo01324b · Cited by 20
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“It is characterized by lipoprotein-rich drusen deposits that form in the subretinal space and the recruitment of immune cells, such as microglia and macrophages (4, 5).”
BackgroundGu, B. J., Huang, X., Avula, P. K., Caruso, E., Drysdale, C., Vessey, K. A., Ou, A., Fowler, C. J., Liu, T.-H., Lin, Y. Q., et al. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.634177 · Cited by 20
“While much data has established a major role of the RPE in phagocytosis of products generated from the turnover of photoreceptor outer segments, mononuclear phagocytes including monocytes and retinal microglia in the subretinal space also perform a phagocytic function and express scavenger receptors including CD36 (17…”
BackgroundSD-OCT assessment of macular and optic nerve alterations in patients recovered from COVID-19
Yıldız, A. M., Gündüz, G. U., Yalçınbayır, Ö., Öztürk, N. A. A., Avcı, R., & Çoşkun, F. (2021) · Canadian Journal of Ophthalmology · doi:10.1016/j.jcjo.2021.06.019 · Cited by 19
“Accumulation of microglia in the outer retina and the subretinal space is thought to be involved in the pathogenesis of chronic neurodegenerative diseases of the retina, such as age-related macular degeneration, diabetic retinopathy and retinal dystrophies.(22) 24 Accordingly, interferonmediated immune response has sh…”
BackgroundHomeostasis and dyshomeostasis of the retina
Zhang, C.-J., & Jin, Z. (2023) · Current Medicine · doi:10.1007/s44194-023-00021-6 · Cited by 25
Droho, S., Voigt, A. P., Sterling, J. K., Rajesh, A., Chan, K. S., Cuda, C. M., Perlman, H., & Lavine, J. A. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02928-1 · Cited by 20
“Therefore, the increased laser-induced CNV area found in Cx3cr1 − / − mice [21] is possibly related to microglia dysregulation.”
BackgroundPrea, S. M., Chan, E. C., Dusting, G. J., Vingrys, A. J., Bui, B. V., & Liu, G. (2015) · Journal of Ophthalmology · doi:10.1155/2015/201726 · Cited by 21
Thrombospondin-1 and Pathogenesis of Age-Related Macular Degeneration
Housset, M., & Sennlaub, F. (2015) · Journal of Ocular Pharmacology and Therapeutics · doi:10.1089/jop.2015.0023 · Cited by 21
Self-citationChemokine Receptor Profiles of T Cells in Patients with Age-Related Macular Degeneration
Choi, Y. J., Lim, D., Byeon, S. H., Shin, E., & Chung, H. (2022) · Yonsei Medical Journal · doi:10.3349/ymj.2022.63.4.357 · Cited by 18
Alfaar, A. S., Stürzbecher, L., Diedrichs‐Möhring, M., Lam, M., Roubeix, C., Ritter, J. M., Schumann, K., Annamalai, B., Pompös, I.-M., Rohrer, B., et al. (2022) · Journal of Neuroinflammation · doi:10.1186/s12974-022-02620-w · Cited by 18
“These mice develop agedependent subretinal inflammation, a hallmark for AMD [11, 15, 74].”
BackgroundSelf-citationP2X7-dependent immune pathways in retinal diseases
Déchelle-Marquet, P.-A., Guillonneau, X., Sennlaub, F., & Delarasse, C. (2022) · Neuropharmacology · doi:10.1016/j.neuropharm.2022.109332 · Cited by 20
Self-citationAge-dependent changes on fractalkine forms and their contribution to neurodegenerative diseases
Eugenín, J. L., Bernhardi, L. E.-V., & Rommy von Bernhardi, M. (2023) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2023.1249320 · Cited by 19
“Interestingly, aged albino mice with Cx3cr1 deletion exhibit, in regions of retinal degeneration, accumulation of microglia in the subretinal space associated with drusen-like yellowish-white dots, and increased choroidal neovascularization, histological findings like those found in patients with AMD (Combadiere et al…”
InfluentialBloomfield, C. L., Gong, J., Droho, S., Makinde, H. M., Gurra, M. G., Stumpf, C. H., Kharel, A., Gadhvi, G. T., Winter, D. R., Cui, W., et al. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1399989 · Cited by 18
“Microglia are known to express ApoE, and alterations in microglia function lead to exacerbated AMD phenotypes (17).”
BackgroundZhang, R., Wang, L., Wang, Y.-F., Wu, C., Lei, C.-L., Wang, M., & Ma, L. (2015) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.15-16830 · Cited by 18
Crowley, M. A., Delgado, O., Will-Orrego, A., Buchanan, N. M., Anderson, K., JAFFEE, B. D., Dryja, T. P., & Liao, S.-M. (2018) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.17-22605 · Cited by 18
Zhang, P., Schlecht, A., Wolf, J., Boneva, S., Laich, Y., Koch, J., Ludwig, F., Boeck, M., Thien, A., Härdtner, C., et al. (2021) · Journal of Neuroinflammation · doi:10.1186/s12974-021-02230-y · Cited by 18
“In the laser-induced CNV model, which mimics aspects of neovascular AMD, we found significantly increased CNV lesion size under Irf8-deficient conditions.”
BackgroundInfluentialClock Gene Nr1d1 Alleviates Retinal Inflammation Through Repression of Hmga2 in Microglia
Wang, Z., Huang, Y., Chu, F., Ji, S., Liao, K., Cui, Z., Chen, J., & Tang, S. (2021) · Journal of Inflammation Research · doi:10.2147/jir.s326091 · Cited by 17
Liisborg, C., Skov, V., Kjær, L., Hasselbalch, H. C., & Sørensen, T. L. (2021) · EClinicalMedicine · doi:10.1016/j.eclinm.2021.101248 · Cited by 18
Hernández, M., Recalde, S., García‐García, L., Bezunartea, J., Miskey, C., Johnen, S., Diarra, S., Sebe, A., Rodríguez-Madoz, J. R., Pouillot, S., et al. (2019) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2019.10.013 · Cited by 18
CD36 Deficiency Inhibits Retinal Inflammation and Retinal Degeneration in Cx3cr1 Knockout Mice
Lavalette, S., Conart, J., Touhami, S., Roubeix, C., Houssier, M., Augustin, S., Raoul, W., Combadière, C., Febbraio, M., Ong, H., et al. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2019.03032 · Cited by 18
“The age-dependent accumulation of subretinal Cx3cr1-deficient MPs is associated with a significant degeneration of rods and cones (5, 29, 30), but not with RPE atrophy.”
BackgroundMethodInfluentialSelf-citationCX3CL1 Regulation of Gliosis in Neuroinflammatory and Neuroprotective Processes
Gutiérrez, I. L., Martín‐Hernández, D., MacDowell, K. S., García‐Bueno, B., Caso, J. R., Leza, J. C., & Madrigal, J. L. M. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26030959 · Cited by 20
Hinnerskov, J. M. V., Nielsen, M. K., Thomsen, A. K., Steffensen, M. A., Honoré, B., Vorum, H., Nissen, M. H., & Sørensen, T. L. (2024) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.65.1.5 · Cited by 17
Reichenbach, A., & Bringmann, A. (2015) · Colloquium Series on Neuroglia in Biology and Medicine From Physiology to Disease · doi:10.4199/c00122ed1v01y201412ngl003 · Cited by 18
Camelo, S., Calippe, B., Lavalette, S., Dominguez, E., Hur, J. C., Devêvre, E., Guillonneau, X., Raoul, W., & Sennlaub, F. (2015) · PubMed Central · Cited by 17
Self-citationDu, X., Peñalva, R. G., Little, K., Kissenpfennig, A., Chen, M., & Xu, H. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00432-9 · Cited by 16
Shi, Q., Wang, Q., Li, J., Zhou, X., Fan, H., Wang, F., Liu, H., Sun, X., & Sun, X. (2015) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.15-17677 · Cited by 16
Meyer, J. H., Cunea, A., Licha, K., Welker, P., Sonntag‐Bensch, D., Wafula, P. O., Dernedde, J., Fimmers, R., Holz, F. G., & Schmitz-Valckenberg, S. (2016) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.15-18118 · Cited by 16
Szczepan, M., Llorián‐Salvador, M., Yi, C., Hughes, D., Mack, M., Chen, M., & Xu, H. (2025) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.66.3.41 · Cited by 16
“9 Phagocyte accumulation in the subretinal space has been observed in the normal aging retina 2,10,11 and models of AMD 12,13 .”
Sharma, N. K., Sharma, K., Singh, R., Sharma, S., & Anand, A. (2018) · PLoS ONE · doi:10.1371/journal.pone.0193423 · Cited by 15
Takahashi, K., Nakamura, S., Otsu, W., Shimazawa, M., & Hara, H. (2021) · Journal of Neuroinflammation · doi:10.1186/s12974-021-02203-1 · Cited by 15
“Expression level of PGRN in eyes of CNV mouse model To examine the pathological role of PGRN in the eye, we performed laser photocoagulation to induce the development of CNVs [18] in adult C57BL/6J mice.”
BackgroundInfluentialAge-Related Macular Degeneration: A Scientometric Analysis.
Ramin, S., Soheilian, M., Habibi, G., Ghazavi, R., Gharebaghi, R., & Heidary, F. (2015) · Medical Hypothesis Discovery & Innovation in Ophthalmology · Cited by 15
Animal models of age-related macular degeneration
Goverdhan, S., Thomson, H. A., & Lotery, A. J. (2013) · Drug Discovery Today Disease Models · doi:10.1016/j.ddmod.2014.03.002 · Cited by 15
Frederick, P. A., & Kleinman, M. E. (2014) · Current Ophthalmology Reports · doi:10.1007/s40135-013-0037-x · Cited by 18
Protective inflammasome activation in AMD
Chen, J., & Smith, L. E. H. (2012) · Nature Medicine · doi:10.1038/nm.2761 · Cited by 16
“Previous studies have focused on the chemotaxis and drusen-derived activation of inflammatory cells in AMD (Combadière et al., 2007;Doyle et al., 2012).”
BackgroundZhu, Y., Aredo, B., Chen, B., Zhao, C. X., He, Y.-G., & Ufret-Vincenty, R. L. (2019) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.19-27212 · Cited by 15
Potential Role of Myeloid-Derived Suppressor Cells (MDSCs) in Age-Related Macular Degeneration (AMD)
Kauppinen, A., Kaarniranta, K., & Salminen, A. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00384 · Cited by 15
“Dysfunctionality or loss of CX3CR1 results in the subretinal accumulation of microglia, which contributes to drusen-like lesions, retinal degeneration, and neovascularization (40).”
BackgroundLee, S., Kim, S., & Jeon, J. S. (2022) · Lab on a Chip · doi:10.1039/d2lc00672c · Cited by 14
Yu, H., Shen, B., Han, R., Zhang, Y., Xu, S., Zhang, Y., Guo, Y., Huang, P., Huang, S., & Zhong, Y. (2024) · Inflammation and Regeneration · doi:10.1186/s41232-024-00343-4 · Cited by 15
CX3C chemokine: Hallmarks of fibrosis and ageing
Chen, X., Yang, Y., Sun, S., Liu, Q., Yang, Y., & Jiang, L. (2024) · Pharmacological Research · doi:10.1016/j.phrs.2024.107348 · Cited by 13
Zhu, M., Jiang, L., Yuan, Y., Chen, L., Liu, X., Liang, J., Zhu, Q., Ding, D., & Song, E. (2019) · Cell and Tissue Research · doi:10.1007/s00441-019-03001-1 · Cited by 14
Badia, A. C., Salas, A., Duarri, A., Ferreira-de-Souza, B., Zapata, M. Á., Fontrodona, L., & García‐Arumí, J. (2020) · Experimental Eye Research · doi:10.1016/j.exer.2020.108424 · Cited by 14
Shihabuddeen, W. A., Yu, R. M. C., Pan, Y., Iwata, T., Barathi, V. A., Wey, Y. S., Tun, S. B. B., Qiu, B., Tan, A., Wang, X., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231810206 · Cited by 14
Loinard, C., Benadjaoud, M. A., L’Homme, B., Flamant, S., Baijer, J., & Tamarat, R. (2023) · Communications Biology · doi:10.1038/s42003-023-04939-3 · Cited by 14
“CCR2 and CX3CR1 have been shown to control monocyte recruitment to ischemic tissues 30,44 .”
BackgroundHebron, M. L., Algarzae, N. K., Lonskaya, I., & Moussa, C. (2013) · Experimental Neurology · doi:10.1016/j.expneurol.2013.01.009 · Cited by 14
Hu, J., Yuan, Y., Shen, L., Zhang, J., Hu, N., & Guan, H. (2011) · Ophthalmic Epidemiology · doi:10.3109/09286586.2011.574335 · Cited by 14
Darbandi-Tehrani, K., Hermand, P., Carvalho, S., Dorgham, K., Couvineau, A., Lacapère, J.-J., Combadière, C., & Déterre, P. (2010) · The FASEB Journal · doi:10.1096/fj.10-156612 · Cited by 13
“The same alleles are associated with an increased risk of cerebrovascular diseases (25) and age-related macular degeneration (12) and a faster progression to AIDS among HIV-1-infected populations (19).”
BackgroundSelf-citationXu, Y., Fu, L., Jiang, C., Qin, Y., Ni, Y., & Fan, J. (2012) · Journal of International Medical Research · doi:10.1177/147323001204000422 · Cited by 14
Fan, Q., & Li, Z. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1703382 · Cited by 16
“CX3CR1-dependent microglial accumulation in the subretinal space is associated with AMD pathology in both human specimens and murine models (13).”
InfluentialMyeloid masquerade: Microglial transcriptional signatures in retinal development and disease
Pitts, K. M., & Margeta, M. A. (2023) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2023.1106547 · Cited by 14
“This transcriptional profile, termed the MGnD, highlighted several key genes shared with the DAM signature (e.g., ApoE, Trem2, Spp1, Clec7a) with increased attention to proinflammatory mediators such as Ccl2.”
BackgroundResultInfluential
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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