{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T07:31:14Z","timestamp":1782977474329,"version":"3.54.5"},"reference-count":94,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2022,5,5]],"date-time":"2022-05-05T00:00:00Z","timestamp":1651708800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2022,5,5]],"date-time":"2022-05-05T00:00:00Z","timestamp":1651708800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"funder":[{"DOI":"10.13039\/100008097","name":"Edward N. and Della L. Thome Memorial Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008097","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000862","name":"Doris Duke Charitable Foundation","doi-asserted-by":"publisher","award":["Clinical Scientist Development Award"],"award-info":[{"award-number":["Clinical Scientist Development Award"]}],"id":[{"id":"10.13039\/100000862","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Reynold and Michiko Spector Award in Neuroscience"},{"name":"William R. Orthwein, Jr. \u201838 Yale Scholar Fund"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Semin Immunopathol"],"published-print":{"date-parts":[[2022,9]]},"DOI":"10.1007\/s00281-022-00939-3","type":"journal-article","created":{"date-parts":[[2022,5,5]],"date-time":"2022-05-05T18:04:28Z","timestamp":1651773868000},"page":"673-683","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Glial-mediated neuroinflammatory mechanisms in age-related macular degeneration"],"prefix":"10.1007","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2014-7515","authenticated-orcid":false,"given":"Rahul M.","family":"Dhodapkar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8839-1864","authenticated-orcid":false,"given":"Diego","family":"Martell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9263-3037","authenticated-orcid":false,"given":"Brian P.","family":"Hafler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,5,5]]},"reference":[{"key":"939_CR1","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1038\/s41572-021-00265-2","volume":"7","author":"M Fleckenstein","year":"2021","unstructured":"Fleckenstein M, Keenan TDL, Guymer RH, Chakravarthy U, Schmitz-Valckenberg S, Klaver CC et al (2021) Age-related macular degeneration. Nat Rev Dis Primers 7:31","journal-title":"Nat Rev Dis Primers"},{"key":"939_CR2","doi-asserted-by":"publisher","first-page":"e106","DOI":"10.1016\/S2214-109X(13)70145-1","volume":"2","author":"WL Wong","year":"2014","unstructured":"Wong WL, Su X, Li X, Cheung CMG, Klein R, Cheng C-Y et al (2014) Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health 2:e106\u2013e116","journal-title":"Lancet Glob Health"},{"key":"939_CR3","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1136\/bjophthalmol-2011-300539","volume":"96","author":"D Pascolini","year":"2012","unstructured":"Pascolini D, Mariotti SP (2012) Global estimates of visual impairment: 2010. Br J Ophthalmol 96:614\u2013618","journal-title":"Br J Ophthalmol"},{"key":"939_CR4","doi-asserted-by":"publisher","first-page":"794","DOI":"10.1001\/jama.2020.5576","volume":"324","author":"U Chakravarthy","year":"2020","unstructured":"Chakravarthy U, Peto T (2020) Current perspective on age-related macular degeneration. JAMA 324:794\u2013795","journal-title":"JAMA"},{"key":"939_CR5","doi-asserted-by":"publisher","first-page":"1579","DOI":"10.2147\/CIA.S142685","volume":"12","author":"A Garc\u00eda-Layana","year":"2017","unstructured":"Garc\u00eda-Layana A, Cabrera-L\u00f3pez F, Garc\u00eda-Arum\u00ed J, Arias-Barquet L, Ruiz-Moreno JM (2017) Early and intermediate age-related macular degeneration: update and clinical review. Clin Interv Aging 12:1579\u20131587","journal-title":"Clin Interv Aging"},{"key":"939_CR6","first-page":"74","volume":"59","author":"A Gheorghe","year":"2015","unstructured":"Gheorghe A, Mahdi L, Musat O (2015) Age-related macular degeneration. Rom J Ophthalmol 59:74\u201377","journal-title":"Rom J Ophthalmol"},{"key":"939_CR7","first-page":"171","volume":"10","author":"RA Armstrong","year":"2015","unstructured":"Armstrong RA, Mousavi M (2015) Overview of risk factors for age-related macular degeneration (AMD). J Stem Cells 10:171\u2013191","journal-title":"J Stem Cells"},{"key":"939_CR8","doi-asserted-by":"publisher","first-page":"1417","DOI":"10.1001\/archopht.119.10.1417","volume":"119","author":"Age-Related Eye Disease Study Research Group","year":"2001","unstructured":"Age-Related Eye Disease Study Research Group (2001) A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Arch Ophthalmol. 119:1417\u20131436","journal-title":"Arch Ophthalmol."},{"key":"939_CR9","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1016\/j.ajpath.2012.06.006","volume":"181","author":"LA Kim","year":"2012","unstructured":"Kim LA, D\u2019Amore PA (2012) A brief history of anti-VEGF for the treatment of ocular angiogenesis. Am J Pathol 181:376\u2013379","journal-title":"Am J Pathol"},{"key":"939_CR10","doi-asserted-by":"publisher","first-page":"1419","DOI":"10.1056\/NEJMoa054481","volume":"355","author":"PJ Rosenfeld","year":"2006","unstructured":"Rosenfeld PJ, Brown DM, Heier JS, Boyer DS, Kaiser PK, Chung CY et al (2006) Ranibizumab for neovascular age-related macular degeneration. N Engl J Med 355:1419\u20131431","journal-title":"N Engl J Med"},{"key":"939_CR11","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1177\/1120672119832432","volume":"29","author":"Z Papadopoulos","year":"2019","unstructured":"Papadopoulos Z (2019) Aflibercept: a review of its effect on the treatment of exudative age-related macular degeneration. Eur J Ophthalmol 29:368\u2013378","journal-title":"Eur J Ophthalmol"},{"key":"939_CR12","first-page":"624","volume":"41","author":"NM Bressler","year":"2000","unstructured":"Bressler NM, Bressler SB (2000) Photodynamic therapy with verteporfin (Visudyne): impact on ophthalmology and visual sciences. Invest Ophthalmol Vis Sci 41:624\u2013628","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"939_CR13","doi-asserted-by":"publisher","unstructured":"Virgili G, Bini A (2007) Laser photocoagulation for neovascular age-related macular degeneration. Cochrane Database Syst Rev\u00a0(3):CD004763.\u00a0https:\/\/doi.org\/10.1002\/14651858.CD004763","DOI":"10.1002\/14651858.CD004763"},{"key":"939_CR14","doi-asserted-by":"publisher","unstructured":"Eandi CM, Giansanti F, Virgili G (2008) Macular translocation for neovascular age-related macular degeneration. Cochrane Database Syst Rev\u00a0(4):CD006928. https:\/\/doi.org\/10.1002\/14651858.CD006928","DOI":"10.1002\/14651858.CD006928"},{"key":"939_CR15","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1186\/s12920-020-00760-7","volume":"13","author":"TW Winkler","year":"2020","unstructured":"Winkler TW, Grassmann F, Brandl C, Kiel C, G\u00fcnther F, Strunz T et al (2020) Genome-wide association meta-analysis for early age-related macular degeneration highlights novel loci and insights for advanced disease. BMC Med Genomics 13:120","journal-title":"BMC Med Genomics"},{"key":"939_CR16","doi-asserted-by":"publisher","first-page":"4902","DOI":"10.1038\/s41467-019-12780-8","volume":"10","author":"M Menon","year":"2019","unstructured":"Menon M, Mohammadi S, Davila-Velderrain J, Goods BA, Cadwell TD, Xing Y et al (2019) Single-cell transcriptomic atlas of the human retina identifies cell types associated with age-related macular degeneration. Nat Commun 10:4902","journal-title":"Nat Commun"},{"key":"939_CR17","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1159\/000490153","volume":"241","author":"T Mimura","year":"2019","unstructured":"Mimura T, Funatsu H, Noma H, Shimura M, Kamei Y, Yoshida M et al (2019) Aqueous humor levels of cytokines in patients with age-related macular degeneration. Ophthalmologica 241:81\u201389","journal-title":"Ophthalmologica"},{"key":"939_CR18","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1007\/s00417-014-2738-8","volume":"253","author":"K Nassar","year":"2015","unstructured":"Nassar K, Grisanti S, Elfar E, L\u00fcke J, L\u00fcke M, Grisanti S (2015) Serum cytokines as biomarkers for age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 253:699\u2013704","journal-title":"Graefes Arch Clin Exp Ophthalmol"},{"key":"939_CR19","doi-asserted-by":"publisher","first-page":"768","DOI":"10.1002\/glia.23727","volume":"68","author":"A Reichenbach","year":"2020","unstructured":"Reichenbach A, Bringmann A (2020) Glia of the human retina. Glia 68:768\u2013796","journal-title":"Glia"},{"key":"939_CR20","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.preteyeres.2014.06.003","volume":"42","author":"M Hoon","year":"2014","unstructured":"Hoon M, Okawa H, Della Santina L, Wong ROL (2014) Functional architecture of the retina: development and disease. Prog Retin Eye Res 42:44\u201384","journal-title":"Prog Retin Eye Res"},{"key":"939_CR21","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1038\/nrn3723","volume":"15","author":"D Goldman","year":"2014","unstructured":"Goldman D (2014) M\u00fcller glial cell reprogramming and retina regeneration. Nat Rev Neurosci 15:431\u2013442","journal-title":"Nat Rev Neurosci"},{"key":"939_CR22","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1126\/science.1194637","volume":"330","author":"F Ginhoux","year":"2010","unstructured":"Ginhoux F, Greter M, Leboeuf M, Nandi S, See P, Gokhan S et al (2010) Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science 330:841\u2013845","journal-title":"Science"},{"key":"939_CR23","doi-asserted-by":"publisher","first-page":"1975","DOI":"10.3389\/fimmu.2019.01975","volume":"10","author":"K Rashid","year":"2019","unstructured":"Rashid K, Akhtar-Schaefer I, Langmann T (2019) Microglia in retinal degeneration. Front Immunol 10:1975","journal-title":"Front Immunol"},{"key":"939_CR24","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.pneurobio.2018.05.006","volume":"173","author":"G Rathnasamy","year":"2019","unstructured":"Rathnasamy G, Foulds WS, Ling E-A, Kaur C (2019) Retinal microglia\u2014a key player in healthy and diseased retina. Prog Neurobiol 173:18\u201340","journal-title":"Prog Neurobiol"},{"key":"939_CR25","doi-asserted-by":"publisher","first-page":"9989","DOI":"10.1073\/pnas.1820387116","volume":"116","author":"Y Okunuki","year":"2019","unstructured":"Okunuki Y, Mukai R, Nakao T, Tabor SJ, Butovsky O, Dana R et al (2019) Retinal microglia initiate neuroinflammation in ocular autoimmunity. Proc Natl Acad Sci USA 116:9989\u20139998","journal-title":"Proc Natl Acad Sci U S A"},{"key":"939_CR26","doi-asserted-by":"publisher","first-page":"472","DOI":"10.3389\/fncel.2019.00472","volume":"13","author":"MDM Fern\u00e1ndez-Arjona","year":"2019","unstructured":"Fern\u00e1ndez-Arjona MDM, Grondona JM, Fern\u00e1ndez-Llebrez P, L\u00f3pez-\u00c1valos MD (2019) Microglial morphometric parameters correlate with the expression level of IL-1\u03b2, and allow identifying different activated morphotypes. Front Cell Neurosci 13:472","journal-title":"Front Cell Neurosci"},{"key":"939_CR27","doi-asserted-by":"publisher","unstructured":"Franco-Bocanegra DK, McAuley C, Nicoll JAR, Boche D (2019) Molecular mechanisms of microglial motility: changes in ageing and Alzheimer\u2019s disease. Cells 8. https:\/\/doi.org\/10.3390\/cells8060639","DOI":"10.3390\/cells8060639"},{"key":"939_CR28","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1016\/S0014-4835(02)00332-9","volume":"76","author":"N Gupta","year":"2003","unstructured":"Gupta N, Brown KE, Milam AH (2003) Activated microglia in human retinitis pigmentosa, late-onset retinal degeneration, and age-related macular degeneration. Exp Eye Res 76:463\u2013471","journal-title":"Exp Eye Res"},{"key":"939_CR29","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1097\/ICU.0b013e32835f8bf8","volume":"24","author":"M Adhi","year":"2013","unstructured":"Adhi M, Duker JS (2013) Optical coherence tomography\u2014current and future applications. Curr Opin Ophthalmol 24:213\u2013221","journal-title":"Curr Opin Ophthalmol"},{"key":"939_CR30","doi-asserted-by":"publisher","first-page":"1774","DOI":"10.1016\/j.ophtha.2020.03.024","volume":"127","author":"E Pilotto","year":"2020","unstructured":"Pilotto E, Miante S, Torresin T, Puthenparampil M, Frizziero L, Federle L et al (2020) Hyperreflective foci in the retina of active relapse-onset multiple sclerosis. Ophthalmology 127:1774\u20131776","journal-title":"Ophthalmology"},{"key":"939_CR31","first-page":"6648191","volume":"2021","author":"J Wu","year":"2021","unstructured":"Wu J, Zhang C, Yang Q, Xie H, Zhang J, Qiu Q et al (2021) Imaging hyperreflective foci as an inflammatory biomarker after anti-VEGF treatment in neovascular age-related macular degeneration patients with optical coherence tomography angiography. Biomed Res Int 2021:6648191","journal-title":"Biomed Res Int"},{"key":"939_CR32","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1038\/cr.2009.139","volume":"20","author":"JR Dunkelberger","year":"2010","unstructured":"Dunkelberger JR, Song W-C (2010) Complement and its role in innate and adaptive immune responses. Cell Res 20:34\u201350","journal-title":"Cell Res"},{"key":"939_CR33","doi-asserted-by":"publisher","first-page":"1456","DOI":"10.1126\/science.1202529","volume":"333","author":"RC Paolicelli","year":"2011","unstructured":"Paolicelli RC, Bolasco G, Pagani F, Maggi L, Scianni M, Panzanelli P et al (2011) Synaptic pruning by microglia is necessary for normal brain development. Science 333:1456\u20131458","journal-title":"Science"},{"key":"939_CR34","doi-asserted-by":"publisher","first-page":"1164","DOI":"10.1016\/j.cell.2007.10.036","volume":"131","author":"B Stevens","year":"2007","unstructured":"Stevens B, Allen NJ, Vazquez LE, Howell GR, Christopherson KS, Nouri N et al (2007) The classical complement cascade mediates CNS synapse elimination. Cell 131:1164\u20131178","journal-title":"Cell"},{"key":"939_CR35","doi-asserted-by":"publisher","first-page":"2827","DOI":"10.1523\/JNEUROSCI.3575-15.2016","volume":"36","author":"X Wang","year":"2016","unstructured":"Wang X, Zhao L, Zhang J, Fariss RN, Ma W, Kretschmer F et al (2016) Requirement for microglia for the maintenance of synaptic function and integrity in the mature retina. J Neurosci 36:2827\u20132842","journal-title":"J Neurosci"},{"key":"939_CR36","doi-asserted-by":"publisher","first-page":"1342","DOI":"10.1042\/BST0381342","volume":"38","author":"SJ Clark","year":"2010","unstructured":"Clark SJ, Bishop PN, Day AJ (2010) Complement factor H and age-related macular degeneration: the role of glycosaminoglycan recognition in disease pathology. Biochem Soc Trans 38:1342\u20131348","journal-title":"Biochem Soc Trans"},{"key":"939_CR37","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1126\/science.1110359","volume":"308","author":"JL Haines","year":"2005","unstructured":"Haines JL, Hauser MA, Schmidt S, Scott WK, Olson LM, Gallins P et al (2005) Complement factor H variant increases the risk of age-related macular degeneration. Science 308:419\u2013421","journal-title":"Science"},{"key":"939_CR38","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/s12974-016-0776-3","volume":"14","author":"S Micklisch","year":"2017","unstructured":"Micklisch S, Lin Y, Jacob S, Karlstetter M, Dannhausen K, Dasari P et al (2017) Age-related macular degeneration associated polymorphism rs10490924 in ARMS2 results in deficiency of a complement activator. J Neuroinflammation 14:4","journal-title":"J Neuroinflammation"},{"key":"939_CR39","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1038\/s41433-020-01265-4","volume":"35","author":"X Zhang","year":"2021","unstructured":"Zhang X, Sivaprasad S (2021) Drusen and pachydrusen: the definition, pathogenesis, and clinical significance. Eye 35:121\u2013133","journal-title":"Eye"},{"key":"939_CR40","doi-asserted-by":"publisher","first-page":"AMD160","DOI":"10.1167\/iovs.18-24882","volume":"59","author":"CA Curcio","year":"2018","unstructured":"Curcio CA (2018) Soft drusen in age-related macular degeneration: biology and targeting via the oil spill strategies. Invest Ophthalmol Vis Sci. 59:AMD160\u2013AMD181","journal-title":"Invest Ophthalmol Vis Sci."},{"key":"939_CR41","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/j.exer.2014.09.009","volume":"128","author":"IR Rodriguez","year":"2014","unstructured":"Rodriguez IR, Clark ME, Lee JW, Curcio CA (2014) 7-Ketocholesterol accumulates in ocular tissues as a consequence of aging and is present in high levels in drusen. Exp Eye Res 128:151\u2013155","journal-title":"Exp Eye Res"},{"key":"939_CR42","doi-asserted-by":"publisher","first-page":"9144","DOI":"10.1038\/srep09144","volume":"5","author":"M Indaram","year":"2015","unstructured":"Indaram M, Ma W, Zhao L, Fariss RN, Rodriguez IR, Wong WT (2015) 7-Ketocholesterol increases retinal microglial migration, activation, and angiogenicity: a potential pathogenic mechanism underlying age-related macular degeneration. Sci Rep 5:9144","journal-title":"Sci Rep"},{"key":"939_CR43","doi-asserted-by":"publisher","first-page":"e100985","DOI":"10.1371\/journal.pone.0100985","volume":"9","author":"J-D Huang","year":"2014","unstructured":"Huang J-D, Amaral J, Lee JW, Rodriguez IR (2014) 7-Ketocholesterol-induced inflammation signals mostly through the TLR4 receptor both in vitro and in vivo. PLoS ONE 9:e100985","journal-title":"PLoS ONE"},{"key":"939_CR44","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1093\/aje\/kwr329","volume":"175","author":"MKM Adams","year":"2012","unstructured":"Adams MKM, Simpson JA, Richardson AJ, English DR, Aung KZ, Makeyeva GA et al (2012) Apolipoprotein E gene associations in age-related macular degeneration: the Melbourne Collaborative Cohort Study. Am J Epidemiol 175:511\u2013518","journal-title":"Am J Epidemiol"},{"key":"939_CR45","doi-asserted-by":"publisher","unstructured":"Wang Y, Wang M, Zhang X, Zhang Q, Nie J, Zhang M et al (2016) The association between the lipids levels in blood and risk of age-related macular degeneration. Nutrients 8. https:\/\/doi.org\/10.3390\/nu8100663","DOI":"10.3390\/nu8100663"},{"key":"939_CR46","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1172\/JCI25843","volume":"116","author":"V Luibl","year":"2006","unstructured":"Luibl V, Isas JM, Kayed R, Glabe CG, Langen R, Chen J (2006) Drusen deposits associated with aging and age-related macular degeneration contain nonfibrillar amyloid oligomers. J Clin Invest 116:378\u2013385","journal-title":"J Clin Invest"},{"key":"939_CR47","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1007\/s00702-010-0433-4","volume":"117","author":"CYD Lee","year":"2010","unstructured":"Lee CYD, Landreth GE (2010) The role of microglia in amyloid clearance from the AD brain. J Neural Transm 117:949\u2013960","journal-title":"J Neural Transm"},{"key":"939_CR48","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.1016\/S0140-6736(18)31550-2","volume":"392","author":"P Mitchell","year":"2018","unstructured":"Mitchell P, Liew G, Gopinath B, Wong TY (2018) Age-related macular degeneration. Lancet 392:1147\u20131159","journal-title":"Lancet"},{"key":"939_CR49","doi-asserted-by":"publisher","first-page":"2468","DOI":"10.1093\/hmg\/ddq129","volume":"19","author":"NV Strunnikova","year":"2010","unstructured":"Strunnikova NV, Maminishkis A, Barb JJ, Wang F, Zhi C, Sergeev Y et al (2010) Transcriptome analysis and molecular signature of human retinal pigment epithelium. Hum Mol Genet 19:2468\u20132486","journal-title":"Hum Mol Genet"},{"key":"939_CR50","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1159\/000356513","volume":"6","author":"A Langford-Smith","year":"2014","unstructured":"Langford-Smith A, Keenan TDL, Clark SJ, Bishop PN, Day AJ (2014) The role of complement in age-related macular degeneration: heparan sulphate, a ZIP code for complement factor H? J Innate Immun 6:407\u2013416","journal-title":"J Innate Immun"},{"key":"939_CR51","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1038\/ng1116","volume":"33","author":"ER Neptune","year":"2003","unstructured":"Neptune ER, Frischmeyer PA, Arking DE, Myers L, Bunton TE, Gayraud B et al (2003) Dysregulation of TGF-beta activation contributes to pathogenesis in Marfan syndrome. Nat Genet 33:407\u2013411","journal-title":"Nat Genet"},{"key":"939_CR52","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/j.molcel.2014.03.030","volume":"54","author":"R Chovatiya","year":"2014","unstructured":"Chovatiya R, Medzhitov R (2014) Stress, inflammation, and defense of homeostasis. Mol Cell 54:281\u2013288","journal-title":"Mol Cell"},{"key":"939_CR53","doi-asserted-by":"publisher","first-page":"130181","DOI":"10.1098\/rsob.130181","volume":"3","author":"GK Sheridan","year":"2013","unstructured":"Sheridan GK, Murphy KJ (2013) Neuron-glia crosstalk in health and disease: fractalkine and CX3CR1 take centre stage. Open Biol 3:130181","journal-title":"Open Biol"},{"key":"939_CR54","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1038\/nn1715","volume":"9","author":"AE Cardona","year":"2006","unstructured":"Cardona AE, Pioro EP, Sasse ME, Kostenko V, Cardona SM, Dijkstra IM et al (2006) Control of microglial neurotoxicity by the fractalkine receptor. Nat Neurosci 9:917\u2013924","journal-title":"Nat Neurosci"},{"key":"939_CR55","doi-asserted-by":"publisher","first-page":"e35446","DOI":"10.1371\/journal.pone.0035446","volume":"7","author":"M Zhang","year":"2012","unstructured":"Zhang M, Xu G, Liu W, Ni Y, Zhou W (2012) Role of fractalkine\/CX3CR1 interaction in light-induced photoreceptor degeneration through regulating retinal microglial activation and migration. PLoS ONE 7:e35446","journal-title":"PLoS ONE"},{"key":"939_CR56","doi-asserted-by":"publisher","first-page":"4444","DOI":"10.1167\/iovs.08-3357","volume":"50","author":"KJ Liang","year":"2009","unstructured":"Liang KJ, Lee JE, Wang YD, Ma W, Fontainhas AM, Fariss RN et al (2009) Regulation of dynamic behavior of retinal microglia by CX3CR1 signaling. Invest Ophthalmol Vis Sci 50:4444\u20134451","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"939_CR57","doi-asserted-by":"publisher","first-page":"1297","DOI":"10.1096\/fj.04-1862fje","volume":"18","author":"J Tuo","year":"2004","unstructured":"Tuo J, Smith BC, Bojanowski CM, Meleth AD, Gery I, Csaky KG et al (2004) The involvement of sequence variation and expression of CX3CR1 in the pathogenesis of age-related macular degeneration. FASEB J 18:1297\u20131299","journal-title":"FASEB J"},{"key":"939_CR58","doi-asserted-by":"publisher","first-page":"10140","DOI":"10.1073\/pnas.1901787116","volume":"116","author":"SK Wang","year":"2019","unstructured":"Wang SK, Xue Y, Rana P, Hong CM, Cepko CL (2019) Soluble CX3CL1 gene therapy improves cone survival and function in mouse models of retinitis pigmentosa. Proc Natl Acad Sci USA 116:10140\u201310149","journal-title":"Proc Natl Acad Sci U S A"},{"key":"939_CR59","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.1111\/j.1471-4159.1984.tb12844.x","volume":"43","author":"M Webb","year":"1984","unstructured":"Webb M, Barclay AN (1984) Localisation of the MRC OX-2 glycoprotein on the surfaces of neurones. J Neurochem 43:1061\u20131067","journal-title":"J Neurochem"},{"key":"939_CR60","doi-asserted-by":"publisher","first-page":"3034","DOI":"10.4049\/jimmunol.171.6.3034","volume":"171","author":"GJ Wright","year":"2003","unstructured":"Wright GJ, Cherwinski H, Foster-Cuevas M, Brooke G, Puklavec MJ, Bigler M et al (2003) Characterization of the CD200 receptor family in mice and humans and their interactions with CD200. J Immunol 171:3034\u20133046","journal-title":"J Immunol"},{"key":"939_CR61","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1097\/NEN.0b013e3181964113","volume":"68","author":"N Koning","year":"2009","unstructured":"Koning N, Swaab DF, Hoek RM, Huitinga I (2009) Distribution of the immune inhibitory molecules CD200 and CD200R in the normal central nervous system and multiple sclerosis lesions suggests neuron-glia and glia-glia interactions. J Neuropathol Exp Neurol 68:159\u2013167","journal-title":"J Neuropathol Exp Neurol"},{"key":"939_CR62","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1016\/j.ophtha.2012.11.002","volume":"120","author":"A Singh","year":"2013","unstructured":"Singh A, Falk MK, Hviid TVF, S\u00f8rensen TL (2013) Increased expression of CD200 on circulating CD11b+ monocytes in patients with neovascular age-related macular degeneration. Ophthalmology 120:1029\u20131037","journal-title":"Ophthalmology"},{"key":"939_CR63","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1111\/ceo.13362","volume":"47","author":"M Krogh Nielsen","year":"2019","unstructured":"Krogh Nielsen M, Subhi Y, Molbech CR, Falk MK, Singh A, Nissen MH et al (2019) Patients with a fast progression profile in geographic atrophy have increased CD200 expression on circulating monocytes. Clin Exp Ophthalmol 47:69\u201378","journal-title":"Clin Exp Ophthalmol"},{"key":"939_CR64","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1016\/j.tem.2015.02.007","volume":"26","author":"V Selvaraj","year":"2015","unstructured":"Selvaraj V, Stocco DM (2015) The changing landscape in translocator protein (TSPO) function. Trends Endocrinol Metab 26:341\u2013348","journal-title":"Trends Endocrinol Metab"},{"key":"939_CR65","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.pharmthera.2007.12.004","volume":"118","author":"M-K Chen","year":"2008","unstructured":"Chen M-K, Guilarte TR (2008) Translocator protein 18 kDa (TSPO): molecular sensor of brain injury and repair. Pharmacol Ther 118:1\u201317","journal-title":"Pharmacol Ther"},{"key":"939_CR66","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2019.107816","volume":"188","author":"K Klee","year":"2019","unstructured":"Klee K, Storti F, Barben M, Samardzija M, Langmann T, Dunaief J et al (2019) Systemic knockout of TSPO in mice does not affect retinal morphology, function and susceptibility to degeneration. Exp Eye Res 188:107816","journal-title":"Exp Eye Res"},{"key":"939_CR67","doi-asserted-by":"publisher","unstructured":"Werry EL, Bright FM, Piguet O, Ittner LM, Halliday GM, Hodges JR et al (2019) Recent developments in TSPO PET imaging as a biomarker of neuroinflammation in neurodegenerative disorders. Int J Mol Sci 20. https:\/\/doi.org\/10.3390\/ijms20133161","DOI":"10.3390\/ijms20133161"},{"key":"939_CR68","doi-asserted-by":"publisher","first-page":"3793","DOI":"10.1523\/JNEUROSCI.3153-13.2014","volume":"34","author":"M Wang","year":"2014","unstructured":"Wang M, Wang X, Zhao L, Ma W, Rodriguez IR, Fariss RN et al (2014) Macroglia-microglia interactions via TSPO signaling regulates microglial activation in the mouse retina. J Neurosci 34:3793\u20133806","journal-title":"J Neurosci"},{"key":"939_CR69","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1186\/s12974-019-1424-5","volume":"16","author":"K Mages","year":"2019","unstructured":"Mages K, Grassmann F, J\u00e4gle H, Rupprecht R, Weber BHF, Hauck SM et al (2019) The agonistic TSPO ligand XBD173 attenuates the glial response thereby protecting inner retinal neurons in a murine model of retinal ischemia. J Neuroinflammation 16:43","journal-title":"J Neuroinflammation"},{"key":"939_CR70","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.4103\/1673-5374.133169","volume":"9","author":"H Yao","year":"2014","unstructured":"Yao H, Wang T, Deng J, Liu D, Li X, Deng J (2014) The development of blood-retinal barrier during the interaction of astrocytes with vascular wall cells. Neural Regen Res 9:1047\u20131054","journal-title":"Neural Regen Res"},{"key":"939_CR71","doi-asserted-by":"publisher","first-page":"1538","DOI":"10.1038\/nn2014","volume":"10","author":"B Ajami","year":"2007","unstructured":"Ajami B, Bennett JL, Krieger C, Tetzlaff W, Rossi FMV (2007) Local self-renewal can sustain CNS microglia maintenance and function throughout adult life. Nat Neurosci 10:1538\u20131543","journal-title":"Nat Neurosci"},{"key":"939_CR72","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1186\/s12974-017-0820-y","volume":"14","author":"J Lechner","year":"2017","unstructured":"Lechner J, Chen M, Hogg RE, Toth L, Silvestri G, Chakravarthy U et al (2017) Peripheral blood mononuclear cells from neovascular age-related macular degeneration patients produce higher levels of chemokines CCL2 (MCP-1) and CXCL8 (IL-8). J Neuroinflammation 14:42","journal-title":"J Neuroinflammation"},{"key":"939_CR73","doi-asserted-by":"publisher","first-page":"e22818","DOI":"10.1371\/journal.pone.0022818","volume":"6","author":"M Chen","year":"2011","unstructured":"Chen M, Forrester JV, Xu H (2011) Dysregulation in retinal para-inflammation and age-related retinal degeneration in CCL2 or CCR2 deficient mice. PLoS ONE 6:e22818","journal-title":"PLoS ONE"},{"key":"939_CR74","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1007\/BF02150948","volume":"223","author":"PL Penfold","year":"1985","unstructured":"Penfold PL, Killingsworth MC, Sarks SH (1985) Senile macular degeneration: the involvement of immunocompetent cells. Graefes Arch Clin Exp Ophthalmol 223:69\u201376","journal-title":"Graefes Arch Clin Exp Ophthalmol"},{"key":"939_CR75","doi-asserted-by":"publisher","first-page":"976","DOI":"10.1136\/bjo.2007.129742","volume":"92","author":"M-K Ezzat","year":"2008","unstructured":"Ezzat M-K, Hann CR, Vuk-Pavlovic S, Pulido JS (2008) Immune cells in the human choroid. Br J Ophthalmol 92:976\u2013980","journal-title":"Br J Ophthalmol"},{"key":"939_CR76","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1111\/j.1365-2567.2005.02173.x","volume":"115","author":"N Patel","year":"2005","unstructured":"Patel N, Ohbayashi M, Nugent AK, Ramchand K, Toda M, Chau K-Y et al (2005) Circulating anti-retinal antibodies as immune markers in age-related macular degeneration. Immunology 115:422\u2013430","journal-title":"Immunology"},{"key":"939_CR77","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1007\/BF00920033","volume":"228","author":"PL Penfold","year":"1990","unstructured":"Penfold PL, Provis JM, Furby JH, Gatenby PA, Billson FA (1990) Autoantibodies to retinal astrocytes associated with age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 228:270\u2013274","journal-title":"Graefes Arch Clin Exp Ophthalmol"},{"key":"939_CR78","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1038\/nm1709","volume":"14","author":"JG Hollyfield","year":"2008","unstructured":"Hollyfield JG, Bonilha VL, Rayborn ME, Yang X, Shadrach KG, Lu L et al (2008) Oxidative damage-induced inflammation initiates age-related macular degeneration. Nat Med 14:194\u2013198","journal-title":"Nat Med"},{"key":"939_CR79","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1007\/s12035-010-8110-z","volume":"41","author":"JG Hollyfield","year":"2010","unstructured":"Hollyfield JG, Perez VL, Salomon RG (2010) A hapten generated from an oxidation fragment of docosahexaenoic acid is sufficient to initiate age-related macular degeneration. Mol Neurobiol 41:290\u2013298","journal-title":"Mol Neurobiol"},{"key":"939_CR80","doi-asserted-by":"publisher","first-page":"110392","DOI":"10.1016\/j.mehy.2020.110392","volume":"146","author":"D Kent","year":"2021","unstructured":"Kent D (2021) The pathogenesis of age-related macular degeneration is not inflammatory mediated but is instead due to immunosenescence-related failure of tissue repair. Med Hypotheses 146:110392","journal-title":"Med Hypotheses"},{"key":"939_CR81","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1016\/j.ajo.2014.03.014","volume":"158","author":"RB Nussenblatt","year":"2014","unstructured":"Nussenblatt RB, Lee RWJ, Chew E, Wei L, Liu B, Sen HN et al (2014) Immune responses in age-related macular degeneration and a possible long-term therapeutic strategy for prevention. Am J Ophthalmol 158:5-11.e2","journal-title":"Am J Ophthalmol"},{"key":"939_CR82","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1038\/nature07201","volume":"454","author":"R Medzhitov","year":"2008","unstructured":"Medzhitov R (2008) Origin and physiological roles of inflammation. Nature 454:428\u2013435","journal-title":"Nature"},{"key":"939_CR83","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1016\/j.immuni.2008.04.006","volume":"28","author":"RC Axtell","year":"2008","unstructured":"Axtell RC, Steinman L (2008) Type 1 interferons cool the inflamed brain. Immunity. 28:600\u2013602","journal-title":"Immunity."},{"key":"939_CR84","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1016\/j.immuni.2008.03.011","volume":"28","author":"M Prinz","year":"2008","unstructured":"Prinz M, Schmidt H, Mildner A, Knobeloch K-P, Hanisch U-K, Raasch J et al (2008) Distinct and nonredundant in vivo functions of IFNAR on myeloid cells limit autoimmunity in the central nervous system. Immunity 28:675\u2013686","journal-title":"Immunity"},{"key":"939_CR85","doi-asserted-by":"publisher","first-page":"670","DOI":"10.15252\/emmm.201505994","volume":"8","author":"A L\u00fcckoff","year":"2016","unstructured":"L\u00fcckoff A, Caramoy A, Scholz R, Prinz M, Kalinke U, Langmann T (2016) Interferon-beta signaling in retinal mononuclear phagocytes attenuates pathological neovascularization. EMBO Mol Med 8:670\u2013678","journal-title":"EMBO Mol Med"},{"key":"939_CR86","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1146\/annurev-immunol-102419-035900","volume":"38","author":"S Duan","year":"2020","unstructured":"Duan S, Paulson JC (2020) Siglecs as immune cell checkpoints in disease. Annu Rev Immunol 38:365\u2013395","journal-title":"Annu Rev Immunol"},{"key":"939_CR87","doi-asserted-by":"publisher","first-page":"154","DOI":"10.15252\/emmm.201606627","volume":"9","author":"M Karlstetter","year":"2017","unstructured":"Karlstetter M, Kopatz J, Aslanidis A, Shahraz A, Caramoy A, Linnartz-Gerlach B et al (2017) Polysialic acid blocks mononuclear phagocyte reactivity, inhibits complement activation, and protects from vascular damage in the retina. EMBO Mol Med 9:154\u2013166","journal-title":"EMBO Mol Med"},{"key":"939_CR88","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/j.mce.2010.04.005","volume":"335","author":"AE Coutinho","year":"2011","unstructured":"Coutinho AE, Chapman KE (2011) The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insights. Mol Cell Endocrinol 335:2\u201313","journal-title":"Mol Cell Endocrinol"},{"key":"939_CR89","doi-asserted-by":"publisher","first-page":"e12790","DOI":"10.1111\/acel.12790","volume":"17","author":"L van Olst","year":"2018","unstructured":"van Olst L, Bielefeld P, Fitzsimons CP, de Vries HE, Schouten M (2018) Glucocorticoid-mediated modulation of morphological changes associated with aging in microglia. Aging Cell 17:e12790","journal-title":"Aging Cell"},{"key":"939_CR90","doi-asserted-by":"publisher","first-page":"1546","DOI":"10.1038\/cdd.2013.108","volume":"20","author":"M\u00c1 Carrillo-de Sauvage","year":"2013","unstructured":"Carrillo-de Sauvage M\u00c1, Maatouk L, Arnoux I, Pasco M, Sanz Diez A, Delahaye M et al (2013) Potent and multiple regulatory actions of microglial glucocorticoid receptors during CNS inflammation. Cell Death Differ 20:1546\u20131557","journal-title":"Cell Death Differ"},{"key":"939_CR91","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1159\/000381865","volume":"234","author":"BD Kuppermann","year":"2015","unstructured":"Kuppermann BD, Goldstein M, Maturi RK, Pollack A, Singer M, Tufail A et al (2015) Dexamethasone intravitreal implant as adjunctive therapy to ranibizumab in neovascular age-related macular degeneration: a multicenter randomized controlled trial. Ophthalmologica 234:40\u201354","journal-title":"Ophthalmologica"},{"key":"939_CR92","doi-asserted-by":"publisher","first-page":"e525","DOI":"10.1038\/cddis.2013.54","volume":"4","author":"K Kobayashi","year":"2013","unstructured":"Kobayashi K, Imagama S, Ohgomori T, Hirano K, Uchimura K, Sakamoto K et al (2013) Minocycline selectively inhibits M1 polarization of microglia. Cell Death Dis 4:e525","journal-title":"Cell Death Dis"},{"key":"939_CR93","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1186\/s12974-015-0431-4","volume":"12","author":"R Scholz","year":"2015","unstructured":"Scholz R, Sobotka M, Caramoy A, Stempfl T, Moehle C, Langmann T (2015) Minocycline counter-regulates pro-inflammatory microglia responses in the retina and protects from degeneration. J Neuroinflammation 12:209","journal-title":"J Neuroinflammation"},{"key":"939_CR94","doi-asserted-by":"publisher","first-page":"eaay8514","DOI":"10.1126\/sciadv.aay8514","volume":"6","author":"A Sharma","year":"2020","unstructured":"Sharma A, Sharma R, Zhang Z, Liaw K, Kambhampati SP, Porterfield JE et al (2020) Dense hydroxyl polyethylene glycol dendrimer targets activated glia in multiple CNS disorders. Sci Adv. 6:eaay8514","journal-title":"Sci Adv."}],"container-title":["Seminars in Immunopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00281-022-00939-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00281-022-00939-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00281-022-00939-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,28]],"date-time":"2022-09-28T17:41:42Z","timestamp":1664386902000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00281-022-00939-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,5]]},"references-count":94,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2022,9]]}},"alternative-id":["939"],"URL":"https:\/\/doi.org\/10.1007\/s00281-022-00939-3","relation":{},"ISSN":["1863-2297","1863-2300"],"issn-type":[{"value":"1863-2297","type":"print"},{"value":"1863-2300","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,5]]},"assertion":[{"value":"1 December 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 April 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 May 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All authors declared that they have no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}