The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
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 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
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
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
“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
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VEGF in signaling and disease: beyond discovery and development
Apte, R. S., Chen, D. S., & Ferrara, N. (2019) · Cell · doi:10.1016/j.cell.2019.01.021 · Cited by 2,721
“, 2015), and factors associated with abnormal activation of monocyte derived macrophages and glial cells as they age (Apte et al., 2006; Ban et al., 2018; Combadière et al., 2007; Kelly et al., 2007; Ma and Wong, 2016; Sene et al., 2013).”
BackgroundMechanisms of Age-Related Macular Degeneration
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“A small-scale study (85 case patients and 105 controls) found CX3CR1-I249 and -M280 alleles at a higher frequency in people with AMD than in control subjects.”
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“Subretinal microglia in normal aged mice are Iba-1þCD68þMHC-IIlow (Xu et al., 2008) and arginase-1þ (Xu et al., unpublished observation), similar to those observed in the cx3cr1-deficient mice (Combadiere et al., 2007).”
BackgroundResult
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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