{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T16:35:47Z","timestamp":1777653347839,"version":"3.51.4"},"reference-count":52,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T00:00:00Z","timestamp":1612137600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T00:00:00Z","timestamp":1612137600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Experimental Eye Research"],"published-print":{"date-parts":[[2021,2]]},"DOI":"10.1016\/j.exer.2020.108424","type":"journal-article","created":{"date-parts":[[2020,12,26]],"date-time":"2020-12-26T01:51:13Z","timestamp":1608947473000},"page":"108424","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":13,"special_numbering":"C","title":["Transcriptomics analysis of Ccl2\/Cx3cr1\/Crb1rd8 deficient mice provides new insights into the pathophysiology of progressive retinal degeneration"],"prefix":"10.1016","volume":"203","author":[{"given":"Anna","family":"Badia","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8781-9611","authenticated-orcid":false,"given":"Anna","family":"Salas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4075-5478","authenticated-orcid":false,"given":"Anna","family":"Duarri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B\u00e1rbara","family":"Ferreira-de-Souza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel \u00c1ngel","family":"Zapata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Fontrodona","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9","family":"Garc\u00eda-Arum\u00ed","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.exer.2020.108424_bib1","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s12974-014-0221-4","article-title":"Differences in the distribution, phenotype and gene expression of subretinal microglia\/macrophages in C57BL\/6N (Crb1rd8\/rd8) versus C57BL6\/J (Crb1wt\/wt) mice","volume":"12","author":"Aredo","year":"2015","journal-title":"J. Neuroinflammation"},{"key":"10.1016\/j.exer.2020.108424_bib2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fphar.2018.01280","article-title":"Oxidative stress in age-related macular degeneration: NRF2 as therapeutic target","volume":"9","author":"Bellezza","year":"2018","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.exer.2020.108424_bib3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.preteyeres.2009.08.003","article-title":"The dynamic nature of Bruch's membrane","volume":"29","author":"Booij","year":"2010","journal-title":"Prog. Retin. Eye Res."},{"key":"10.1016\/j.exer.2020.108424_bib4","series-title":"Retinal Degenerative Diseases, Advances in Experimental Medicine and Biology","first-page":"11","article-title":"Mitochondria: potential targets for protection in age-related macular degeneration","author":"Brown","year":"2018"},{"key":"10.1016\/j.exer.2020.108424_bib5","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1159\/000119862","article-title":"Ccl2\/Cx3cr1-deficient mice: an animal model for age-related macular degeneration","volume":"40","author":"Chan","year":"2008","journal-title":"Ophthalmic Res."},{"key":"10.1016\/j.exer.2020.108424_bib6","article-title":"Age- and light-dependent development of localised retinal atrophy in CCL2-\/-CX3CR1GFP\/GFP Mice","volume":"8","author":"Chen","year":"2013","journal-title":"PLoS One"},{"key":"10.1016\/j.exer.2020.108424_bib7","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.preteyeres.2018.10.003","article-title":"Immune regulation in the aging retina","volume":"69","author":"Chen","year":"2019","journal-title":"Prog. Retin. Eye Res."},{"key":"10.1016\/j.exer.2020.108424_bib8","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.1016\/j.ophtha.2017.05.035","article-title":"Prevalence of age-related macular degeneration in europe: the past and the future","volume":"124","author":"Colijn","year":"2017","journal-title":"Ophthalmology"},{"key":"10.1016\/j.exer.2020.108424_bib9","doi-asserted-by":"crossref","first-page":"2920","DOI":"10.1172\/JCI31692","article-title":"CX3CR1-dependent subretinal microglia cell accumulation is associated with cardinal features of age-related macular degeneration","volume":"117","author":"Combadi\u00e8re","year":"2007","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.exer.2020.108424_bib10","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1002\/glia.22942","article-title":"M\u00fcller glia as an important source of cytokines and inflammatory factors present in the gliotic retina during proliferative vitreoretinopathy","volume":"64","author":"Eastlake","year":"2016","journal-title":"Glia"},{"key":"10.1016\/j.exer.2020.108424_bib11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mrrev.2003.11.001","article-title":"Oxidative DNA damage and disease: induction, repair and significance","volume":"567","author":"Evans","year":"2004","journal-title":"Mutat. Res. Rev. Mutat. Res."},{"key":"10.1016\/j.exer.2020.108424_bib12","first-page":"765","article-title":"Expression of CCL2 and its receptor in activation and migration of microglia and monocytes induced by photoreceptor apoptosis","volume":"23","author":"Feng","year":"2017","journal-title":"Mol. Vis."},{"key":"10.1016\/j.exer.2020.108424_bib13","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1038\/ng.3448","article-title":"A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants","volume":"48","author":"Fritsche","year":"2016","journal-title":"Nat. Genet."},{"key":"10.1016\/j.exer.2020.108424_bib14","doi-asserted-by":"crossref","first-page":"3554","DOI":"10.2337\/db15-0180","article-title":"M\u00fcller glia are a major cellular source of survival signals for retinal neurons in diabetes","volume":"64","author":"Fu","year":"2015","journal-title":"Diabetes"},{"key":"10.1016\/j.exer.2020.108424_bib15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2015\/690243","article-title":"NLRP3 inflammasome: activation and regulation in age-related macular degeneration","volume":"2015","author":"Gao","year":"2015","journal-title":"Mediat. Inflamm."},{"key":"10.1016\/j.exer.2020.108424_bib16","series-title":"Retinal Degenerative Diseases, Advances in Experimental Medicine and Biology","first-page":"165","article-title":"Mitochondrial decay and impairment of antioxidant defenses in aging RPE cells","author":"He","year":"2010"},{"key":"10.1016\/j.exer.2020.108424_bib17","doi-asserted-by":"crossref","first-page":"2310","DOI":"10.2353\/ajpath.2009.090023","article-title":"Resident microglia and bone marrow immigrants remove dead photoreceptors in retinal lesions","volume":"174","author":"Joly","year":"2009","journal-title":"Am. J. Pathol."},{"key":"10.1016\/j.exer.2020.108424_bib18","doi-asserted-by":"crossref","first-page":"4106","DOI":"10.1128\/MCB.20.11.4106-4114.2000","article-title":"Analysis of fractalkine receptor CX(3)CR1 function by targeted deletion and green fluorescent protein reporter gene insertion","volume":"20","author":"Jung","year":"2000","journal-title":"Mol. Cell Biol."},{"key":"10.1016\/j.exer.2020.108424_bib19","first-page":"1","article-title":"Complete transcriptome profiling of normal and age-related macular degeneration eye tissues reveals dysregulation of anti-sense transcription","volume":"8","author":"Kim","year":"2018","journal-title":"Sci. Rep."},{"key":"10.1016\/j.exer.2020.108424_bib20","doi-asserted-by":"crossref","first-page":"7166","DOI":"10.1167\/iovs.14-15168","article-title":"Identification of vinculin as a potential plasma marker for age-related macular degeneration","volume":"55","author":"Kim","year":"2014","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.exer.2020.108424_bib21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12974-015-0408-3","article-title":"Expression pattern of Ccr2 and Cx3cr1 in inherited retinal degeneration","volume":"12","author":"Kohno","year":"2015","journal-title":"J. Neuroinflammation"},{"key":"10.1016\/j.exer.2020.108424_bib22","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.exer.2015.04.020","article-title":"The microglia in healthy and diseased retina","volume":"136","author":"Li","year":"2015","journal-title":"Exp. Eye Res."},{"key":"10.1016\/j.exer.2020.108424_bib23","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1016\/S0140-6736(12)60282-7","article-title":"Age-related macular degeneration","volume":"379","author":"Lim","year":"2012","journal-title":"Lancet"},{"key":"10.1016\/j.exer.2020.108424_bib24","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1093\/hmg\/ddu424","article-title":"The severity of retinal pathology in homozygous Crb1rd8\/rd8 mice is dependent on additional genetic factors","volume":"24","author":"Luhmann","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.exer.2020.108424_bib25","author":"Luhmann"},{"key":"10.1016\/j.exer.2020.108424_bib26","doi-asserted-by":"crossref","first-page":"5934","DOI":"10.1167\/iovs.09-3462","article-title":"The drusenlike phenotype in aging Ccl2-knockout mice is caused by an accelerated accumulation of swollen autofluorescent subretinal macrophages","volume":"50","author":"Luhmann","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.exer.2020.108424_bib27","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1056\/NEJM199802123380706","article-title":"C hemokines \u2014 C hemotactic C ytokines T hat M ediate I nflammation","volume":"338","author":"Luster","year":"1998","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.exer.2020.108424_bib28","doi-asserted-by":"crossref","first-page":"2921","DOI":"10.1167\/iovs.12-9662","article-title":"The Rd8 mutation of the Crb1 gene is present in vendor lines of C57BL\/6N mice and embryonic stem cells, and confounds ocular induced mutant phenotypes","volume":"53","author":"Mattapallil","year":"2012","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.exer.2020.108424_bib29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/ijms19010318","article-title":"Microglia and aging: the role of the TREM2\u2013DAP12 and CX3CL1-CX3CR1 Axes","volume":"19","author":"Mecca","year":"2018","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.exer.2020.108424_bib30","doi-asserted-by":"crossref","first-page":"2179","DOI":"10.1093\/hmg\/ddg232","article-title":"CRB1 is essential for external limiting membrane integrity and photoreceptor morphogenesis in the mammalian retina","volume":"12","author":"Mehalow","year":"2003","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.exer.2020.108424_bib31","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.neurobiolaging.2017.09.021","article-title":"The aging rat retina: from function to anatomy","volume":"61","author":"Nadal-Nicol\u00e1s","year":"2018","journal-title":"Neurobiol. Aging"},{"key":"10.1016\/j.exer.2020.108424_bib32","doi-asserted-by":"crossref","DOI":"10.1155\/2014\/930671","article-title":"Age-related macular degeneration in the aspect of chronic low-grade inflammation ( pathophysiological ParaInflammation )","volume":"2014","author":"Nita","year":"2014","journal-title":"Mediat. Inflamm."},{"key":"10.1016\/j.exer.2020.108424_bib33","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1167\/iovs.05-0976","article-title":"Proteomics of the retinal pigment epithelium reveals altered protein expression at progressive stages of age-related macular degeneration","volume":"47","author":"Nordgaard","year":"2006","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.exer.2020.108424_bib34","doi-asserted-by":"crossref","first-page":"2848","DOI":"10.1167\/iovs.07-1352","article-title":"Mitochondrial proteomics of the retinal pigment epithelium at progressive stages of age-related macular degeneration","volume":"49","author":"Nordgaard","year":"2008","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.exer.2020.108424_bib35","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/1742-2094-7-87","article-title":"CCL2\/CCR2 and CX3CL1\/CX3CR1 chemokine axes and their possible involvement in age-related macular degeneration","volume":"7","author":"Raoul","year":"2010","journal-title":"J. Neuroinflammation"},{"key":"10.1016\/j.exer.2020.108424_bib36","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1038\/s41588-019-0351-9","article-title":"Retinal transcriptome and eQTL analyses identify genes associated with age-related macular degeneration","volume":"51","author":"Ratnapriya","year":"2019","journal-title":"Nat. Genet."},{"key":"10.1016\/j.exer.2020.108424_bib37","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/j.exer.2008.01.014","article-title":"Immunological protein expression profile in Ccl2\/Cx3cr1 deficient mice with lesions similar to age-related macular degeneration","volume":"86","author":"Ross","year":"2008","journal-title":"Exp. Eye Res."},{"key":"10.1016\/j.exer.2020.108424_bib38","first-page":"1","article-title":"Incidence of late stage age related macular degeneration in American whites: systematic review and meta-analysis","author":"Rudnicka","year":"2015","journal-title":"Am. J. Ophthalmol."},{"key":"10.1016\/j.exer.2020.108424_bib39","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.exer.2013.10.024","article-title":"Nrf2 signaling is impaired in the aging RPE given an oxidative insult","volume":"119","author":"Sachdeva","year":"2014","journal-title":"Exp. Eye Res."},{"key":"10.1016\/j.exer.2020.108424_bib40","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s40246-019-0199-1","article-title":"Transcriptome-wide analysis of differentially expressed chemokine receptors, SNPs, and SSRs in the age-related macular degeneration","volume":"13","author":"Saddala","year":"2019","journal-title":"Hum. Genom."},{"key":"10.1016\/j.exer.2020.108424_bib41","doi-asserted-by":"crossref","first-page":"7304","DOI":"10.1523\/JNEUROSCI.0190-15.2015","article-title":"Investigating mitochondria as a target for treating age-related macular degeneration","volume":"35","author":"Terluk","year":"2015","journal-title":"J. Neurosci."},{"key":"10.1016\/j.exer.2020.108424_bib42","doi-asserted-by":"crossref","first-page":"3827","DOI":"10.1167\/iovs.07-0051","article-title":"Murine Ccl2\/Cx3cr1 deficiency results in retinal lesions mimicking human age-related macular degeneration","volume":"48","author":"Tuo","year":"2007","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.exer.2020.108424_bib43","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.1002\/glia.20561","article-title":"Crb1 is a determinant of retinal apical m\u00fcller glia cell features","volume":"55","author":"Van de Pavert","year":"2007","journal-title":"Glia"},{"key":"10.1016\/j.exer.2020.108424_bib44","doi-asserted-by":"crossref","first-page":"3659","DOI":"10.1167\/iovs.07-1474","article-title":"Abnormal reactivity of M\u00fcller cells after retinal detachment in mice deficient in GFAP and vimentin","volume":"49","author":"Verardo","year":"2008","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.exer.2020.108424_bib45","doi-asserted-by":"crossref","first-page":"7833","DOI":"10.1167\/iovs.12-10650","article-title":"Ccl2\/Cx3cr1 knockout mice have inner retinal dysfunction but are not an accelerated model of AMD","volume":"53","author":"Vessey","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.exer.2020.108424_bib46","series-title":"Investigative Ophthalmology & Visual Science","article-title":"Genotype at polymorphism rd5749482 and TIMP3 expression in AMD","author":"Wang","year":"2014"},{"key":"10.1016\/j.exer.2020.108424_bib47","first-page":"2834","article-title":"NF-\u03baB activation in light-induced retinal degeneration in a mouse model","volume":"43","author":"Wu","year":"2002","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.exer.2020.108424_bib48","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1111\/j.1474-9726.2007.00351.x","article-title":"Age-dependent accumulation of lipofuscin in perivascular and subretinal microglia in experimental mice","volume":"7","author":"Xu","year":"2008","journal-title":"Aging Cell"},{"key":"10.1016\/j.exer.2020.108424_bib49","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1002\/syn.21674","article-title":"Early degeneration of photoreceptor synapse in ccl2\/cx3cr1 deficient mice on Crb1rd8 background","volume":"67","author":"Zhang","year":"2013","journal-title":"Synapse"},{"key":"10.1016\/j.exer.2020.108424_bib50","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.15252\/emmm.201505298","article-title":"Microglial phagocytosis of living photoreceptors contributes to inherited retinal degeneration","volume":"7","author":"Zhao","year":"2015","journal-title":"EMBO Mol. Med."},{"key":"10.1016\/j.exer.2020.108424_bib51","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fnana.2017.00077","article-title":"Microglia polarization with M1\/M2 phenotype changes in rd1 mouse model of retinal degeneration","volume":"11","author":"Zhou","year":"2017","journal-title":"Front. Neuroanat."},{"key":"10.1016\/j.exer.2020.108424_bib52","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1016\/j.exer.2011.07.017","article-title":"Cellular and 3D optical coherence tomography assessment during the initiation and progression of retinal degeneration in the Ccl2\/Cx3cr1-deficient mouse","volume":"93","author":"Zhou","year":"2011","journal-title":"Exp. Eye Res."}],"container-title":["Experimental Eye Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014483520306825?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014483520306825?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T05:08:52Z","timestamp":1757999332000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0014483520306825"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2]]},"references-count":52,"alternative-id":["S0014483520306825"],"URL":"https:\/\/doi.org\/10.1016\/j.exer.2020.108424","relation":{},"ISSN":["0014-4835"],"issn-type":[{"value":"0014-4835","type":"print"}],"subject":[],"published":{"date-parts":[[2021,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Transcriptomics analysis of Ccl2\/Cx3cr1\/Crb1rd8 deficient mice provides new insights into the pathophysiology of progressive retinal degeneration","name":"articletitle","label":"Article Title"},{"value":"Experimental Eye Research","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.exer.2020.108424","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"108424"}}