{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T02:54:30Z","timestamp":1791428070154,"version":"4.3.3"},"reference-count":70,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,24]],"date-time":"2022-01-24T00:00:00Z","timestamp":1642982400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003493","name":"Gemeinn\u00fctzige Hertie-Stiftung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003493","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007200","name":"Medizinische Fakult\u00e4t, Ruhr-Universit\u00e4t Bochum","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007200","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein-antibody-associated disease (MOGAD) are antibody mediated CNS disorders mostly affecting the optic nerve and spinal cord with potential severe impact on the visual pathway. Here, we investigated inflammation and degeneration of the visual system in a spontaneous encephalomyelitis animal model. We used double-transgenic (2D2\/Th) mice which develop a spontaneous opticospinal encephalomyelitis (OSE). Retinal morphology and its function were evaluated via spectral domain optical coherence tomography (SD-OCT) and electroretinography (ERG) in 6- and 8-week-old mice. Immunohistochemistry of retina and optic nerve and examination of the retina via RT-qPCR were performed using markers for inflammation, immune cells and the complement pathway. OSE mice showed clinical signs of encephalomyelitis with an incidence of 75% at day 38. A progressive retinal thinning was detected in OSE mice via SD-OCT. An impairment in photoreceptor signal transmission occurred. This was accompanied by cellular infiltration and demyelination of optic nerves. The number of microglia\/macrophages was increased in OSE optic nerves and retinas. Analysis of the retina revealed a reduced retinal ganglion cell number and downregulated <jats:italic>Pou4f1<\/jats:italic> mRNA expression in OSE retinas. RT-qPCR revealed an elevation of microglia markers and the cytokines <jats:italic>Tnfa<\/jats:italic> and <jats:italic>Tgfb<\/jats:italic>. We also documented an upregulation of the complement system via the classical pathway. In summary, we describe characteristics of inflammation and degeneration of the visual system in a spontaneous encephalomyelitis model, characterized by coinciding inflammatory and degenerative mechanisms in both retina and optic nerve with involvement of the complement system.<\/jats:p>","DOI":"10.3389\/fimmu.2021.759389","type":"journal-article","created":{"date-parts":[[2022,1,24]],"date-time":"2022-01-24T05:22:40Z","timestamp":1643001760000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Progressive Retinal and Optic Nerve Damage in a Mouse Model of Spontaneous Opticospinal Encephalomyelitis"],"prefix":"10.3389","volume":"12","author":[{"given":"Laura","family":"Petrikowski","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Reinehr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen","family":"Haupeltshofer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonie","family":"Deppe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Graz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingo","family":"Kleiter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. Burkhard","family":"Dick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Gold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Faissner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie C.","family":"Joachim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)61620-7","article-title":"Multiple Sclerosis","volume":"372","author":"Compston","year":"2008","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI15861","article-title":"Myelin\/oligodendrocyte Glycoprotein-Deficient (MOG-Deficient) Mice Reveal Lack of Immune Tolerance to MOG in Wild-Type Mice","volume":"112","author":"Delarasse","year":"2003","journal-title":"J Clin Invest"},{"key":"B3","doi-asserted-by":"publisher","first-page":"577742","DOI":"10.1016\/j.jneuroim.2021.577742","article-title":"Clinicoradiological Comparative Study of Aquaporin-4-IgG Seropositive Neuromyelitis Optica Spectrum Disorder (NMOSD) and MOG Antibody Associated Disease (MOGAD): A Prospective Observational Study and Review of Literature","volume":"361","author":"Nagireddy","year":"2021","journal-title":"J Neuroimmunol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1756286418762083","DOI":"10.1177\/1756286418762083","article-title":"Defining Distinct Features of Anti-MOG Antibody Associated Central Nervous System Demyelination","volume":"11","author":"Weber","year":"2018","journal-title":"Ther Adv Neurol Disord"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1833158100","article-title":"The Crystal Structure of Myelin Oligodendrocyte Glycoprotein, a Key Autoantigen in Multiple Sclerosis","volume":"100","author":"Clements","year":"2003","journal-title":"Proc Natl Acad Sci USA"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2013.5857","article-title":"Neuromyelitis Optica Spectrum Disorders With Aquaporin-4 and Myelin-Oligodendrocyte Glycoprotein Antibodies: A Comparative Study","volume":"71","author":"Kitley","year":"2014","journal-title":"JAMA Neurol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"102399","DOI":"10.1016\/j.msard.2020.102399","article-title":"Clinical and Laboratory Features Distinguishing MOG Antibody Disease From Multiple Sclerosis and AQP4 Antibody-Positive Neuromyelitis Optica","volume":"45","author":"Ciotti","year":"2020","journal-title":"Mult Scler Relat Disord"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1079","DOI":"10.1016\/j.ophtha.2007.08.04","article-title":"Visual Function 15 Years After Optic Neuritis: A Final Follow-Up Report From the Optic Neuritis Treatment Trial","volume":"115","author":"Optic Neuritis Study","year":"2008","journal-title":"Ophthalmology"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1172\/JCI28330","article-title":"Spontaneous Opticospinal Encephalomyelitis in a Double-Transgenic Mouse Model of Autoimmune T Cell\/B Cell Cooperation","volume":"116","author":"Krishnamoorthy","year":"2006","journal-title":"J Clin Invest"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1905955116","article-title":"Smad7 in Intestinal CD4(+) T Cells Determines Autoimmunity in a Spontaneous Model of Multiple Sclerosis","volume":"116","author":"Haupeltshofer","year":"2019","journal-title":"Proc Natl Acad Sci USA"},{"key":"B11","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1186\/s40478-016-0355-y","article-title":"Aquaporin 4-Specific T Cells and NMO-IgG Cause Primary Retinal Damage in Experimental NMO\/SD","volume":"4","author":"Zeka","year":"2016","journal-title":"Acta Neuropathol Commun"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20021603","article-title":"Myelin Oligodendrocyte Glycoprotein-Specific T Cell Receptor Transgenic Mice Develop Spontaneous Autoimmune Optic Neuritis","volume":"197","author":"Bettelli","year":"2003","journal-title":"J Exp Med"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1084\/jem.188.1.169","article-title":"B Lymphocytes Producing Demyelinating Autoantibodies: Development and Function in Gene-Targeted Transgenic Mice","volume":"188","author":"Litzenburger","year":"1998","journal-title":"J Exp Med"},{"key":"B14","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1186\/s12974-018-1208-3","article-title":"Laquinimod Protects the Optic Nerve and Retina in an Experimental Autoimmune Encephalomyelitis Model","volume":"15","author":"Wilmes","year":"2018","journal-title":"J Neuroinflamm"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.10-5551","article-title":"Tracking Longitudinal Retinal Changes in Experimental Ocular Hypertension Using the cSLO and Spectral Domain-OCT","volume":"51","author":"Guo","year":"2010","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"B16","doi-asserted-by":"publisher","first-page":"e96494","DOI":"10.1371\/journal.pone.0096494","article-title":"Spectral-Domain Optical Coherence Tomography of the Rodent Eye: Highlighting Layers of the Outer Retina Using Signal Averaging and Comparison With Histology","volume":"9","author":"Berger","year":"2014","journal-title":"PloS One"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.01381","article-title":"Intravitreal Therapy Against the Complement Factor C5 Prevents Retinal Degeneration in an Experimental Autoimmune Glaucoma Model","volume":"10","author":"Reinehr","year":"2019","journal-title":"Front Pharmacol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1997","DOI":"10.3390\/ijms.22041997","article-title":"Activation of Apoptosis in a Betab1-CTGF Transgenic Mouse Model","volume":"22","author":"Weiss","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B19","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1186\/1742-2094-10-120","article-title":"Inflammatory Demyelination Induces Glia Alterations and Ganglion Cell Loss in the Retina of an Experimental Autoimmune Encephalomyelitis Model","volume":"10","author":"Horstmann","year":"2013","journal-title":"J\u00a0Neuroinflamm"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-017-2710-0","article-title":"HSP27 Immunization Reinforces AII Amacrine Cell and Synapse Damage Induced by S100 in an Autoimmune Glaucoma Model","volume":"371","author":"Reinehr","year":"2018","journal-title":"Cell Tissue Res"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2016.00140","article-title":"Simultaneous Complement Response via Lectin Pathway in Retina and Optic Nerve in an Experimental Autoimmune Glaucoma Model","volume":"10","author":"Reinehr","year":"2016","journal-title":"Front Cell Neurosci"},{"key":"B22","doi-asserted-by":"publisher","first-page":"e36","DOI":"10.1093\/nar\/30.9.e36","article-title":"Relative Expression Software Tool (REST) for Group-Wise Comparison and Statistical Analysis of Relative Expression Results in Real-Time PCR","volume":"30","author":"Pfaffl","year":"2002","journal-title":"Nucleic Acids Res"},{"key":"B23","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.preteyeres.2014.11.004","article-title":"Retinal Microglia: Just Bystander or Target for Therapy","volume":"45","author":"Karlstetter","year":"2015","journal-title":"Prog Retin Eye Res"},{"key":"B24","doi-asserted-by":"publisher","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":"B25","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1525528113","article-title":"New Tools for Studying Microglia in the Mouse and Human CNS","volume":"113","author":"Bennett","year":"2016","journal-title":"Proc Natl Acad Sci USA"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.09-4098","article-title":"RNA Binding Protein With Multiple Splicing: A New Marker for Retinal Ganglion Cells","volume":"51","author":"Kwong","year":"2010","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"B27","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1016\/j.preteyeres.2006.05.003","article-title":"Muller Cells in the Healthy and Diseased Retina","volume":"25","author":"Bringmann","year":"2006","journal-title":"Prog Retin Eye Res"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/120.3.393","article-title":"Axonal Damage in Acute Multiple Sclerosis Lesions","volume":"120","author":"Ferguson","year":"1997","journal-title":"Brain"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199801293380502","article-title":"Axonal Transection in the Lesions of Multiple Sclerosis","volume":"338","author":"Trapp","year":"1998","journal-title":"N Engl J Med"},{"key":"B30","doi-asserted-by":"publisher","first-page":"e193; author reply e194","DOI":"10.1093\/brain\/awr095","article-title":"Primary Retinal Pathology in Multiple Sclerosis as Detected by Optical Coherence Tomography","volume":"134","author":"Brandt","year":"2011","journal-title":"Brain"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awq346","article-title":"Primary Retinal Pathology in Multiple Sclerosis as Detected by Optical Coherence Tomography","volume":"134","author":"Saidha","year":"2011","journal-title":"Brain"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2018.00888","article-title":"Diagnosis and Treatment of NMO Spectrum Disorder and MOG-Encephalomyelitis","volume":"9","author":"Borisow","year":"2018","journal-title":"Front Neurol"},{"key":"B33","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1007\/s00415-017-8651-4","article-title":"Clinical Characteristics of Myelin Oligodendrocyte Glycoprotein Seropositive Optic Neuritis: A Cohort Study in Shanghai, China","volume":"265","author":"Zhao","year":"2018","journal-title":"J Neurol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1177\/1352458513476562","article-title":"Longitudinal Follow-Up of Vision in a Neuromyelitis Optica Cohort","volume":"19","author":"Bouyon","year":"2013","journal-title":"Mult Scler"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181af78b8","article-title":"Optical Coherence Tomography Helps Differentiate Neuromyelitis Optica and MS Optic Neuropathies","volume":"73","author":"Ratchford","year":"2009","journal-title":"Neurology"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1111\/aos.12215","article-title":"Analysis of Spectral Domain Optical Coherence Tomography Measurements in Optic Neuritis: Differences in Neuromyelitis Optica, Multiple Sclerosis, Isolated Optic Neuritis and Normal Healthy Controls","volume":"92","author":"Park","year":"2014","journal-title":"Acta Ophthalmol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1177\/1352458519864928","article-title":"Aquaporin-4 IgG Seropositivity Is Associated With Worse Visual Outcomes After Optic Neuritis Than MOG-IgG Seropositivity and Multiple Sclerosis, Independent of Macular Ganglion Cell Layer Thinning","volume":"26","author":"Sotirchos","year":"2020","journal-title":"Mult Scler"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2020.540156","article-title":"AQP4-IgG and MOG-IgG Related Optic Neuritis-Prevalence, Optical Coherence Tomography Findings, and Visual Outcomes: A Systematic Review and Meta-Analysis","volume":"11","author":"Filippatou","year":"2020","journal-title":"Front Neurol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1055\/a-1219-7907","article-title":"Aquaporin-4 and Myelin Oligodendrocyte Glycoprotein Antibody-Associated Optic Neuritis: Diagnosis and Treatment","volume":"237","author":"Wildemann","year":"2020","journal-title":"Klin Monbl Augenheilkd"},{"key":"B40","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.jaut.2014.09.003","article-title":"Neutralizing IL-17 Protects the Optic Nerve From Autoimmune Pathology and Prevents Retinal Nerve Fiber Layer Atrophy During Experimental Autoimmune Encephalomyelitis","volume":"56","author":"Knier","year":"2015","journal-title":"J Autoimmun"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.149228","article-title":"Distinctive Waves of Innate Immune Response in the Retina in Experimental Autoimmune Encephalomyelitis","volume":"6","author":"Cruz-Herranz","year":"2021","journal-title":"JCI Insight"},{"key":"B42","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1186\/s12974-019-1583-4","article-title":"Monitoring Retinal Changes With Optical Coherence Tomography Predicts Neuronal Loss in Experimental Autoimmune Encephalomyelitis","volume":"16","author":"Cruz-Herranz","year":"2019","journal-title":"J\u00a0Neuroinflamm"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2018.11.010","article-title":"Sequential Phases of RGC Axonal and Somatic Injury in EAE Mice Examined Using DTI and OCT","volume":"27","author":"Nishioka","year":"2019","journal-title":"Mult Scler Relat Disord"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1007\/s10633-006-9022-0","article-title":"Electroretinographic Abnormalities in Multiple Sclerosis: Possible Role for Retinal Autoantibodies","volume":"113","author":"Forooghian","year":"2006","journal-title":"Doc Ophthalmol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2019.01.016","article-title":"Evidence of Muller Glial Dysfunction in Patients With Aquaporin-4 Immunoglobulin G-Positive Neuromyelitis Optica Spectrum Disorder","volume":"126","author":"You","year":"2019","journal-title":"Ophthalmology"},{"key":"B46","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1007\/978-1-4939-7720-8_2","article-title":"Measuring Retinal Function in the Mouse","volume":"1753","author":"Kremers","year":"2018","journal-title":"Methods Mol Biol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.14433","article-title":"Loss of Retinal Ganglion Cells in a New Genetic Mouse Model for Primary Open-Angle Glaucoma","volume":"23","author":"Reinehr","year":"2019","journal-title":"J Cell Mol Med"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2018.06.011","article-title":"Structural and Visual Functional Deficits in a Rat Model of Neuromyelitis Optica Spectrum Disorders Related Optic Neuritis","volume":"175","author":"Zhang","year":"2018","journal-title":"Exp Eye Res"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-16-06214.2001","article-title":"Acute Neuronal Apoptosis in a Rat Model of Multiple Sclerosis","volume":"21","author":"Meyer","year":"2001","journal-title":"J Neurosci"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2004.tb00047.x","article-title":"Mechanisms and Time Course of Neuronal Degeneration in Experimental Autoimmune Encephalomyelitis","volume":"14","author":"Hobom","year":"2004","journal-title":"Brain Pathol"},{"key":"B51","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.jneuroim.2016.06.008","article-title":"Microglia Response in Retina and Optic Nerve in Chronic Experimental Autoimmune Encephalomyelitis","volume":"298","author":"Horstmann","year":"2016","journal-title":"J Neuroimmunol"},{"key":"B52","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1186\/s40478-019-0768-5","article-title":"Retinal Pathology in Experimental Optic Neuritis is Characterized by Retrograde Degeneration and Gliosis","volume":"7","author":"Manogaran","year":"2019","journal-title":"Acta Neuropathol Commun"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awq080","article-title":"Ocular Pathology in Multiple Sclerosis: Retinal Atrophy and Inflammation Irrespective of Disease Duration","volume":"133","author":"Green","year":"2010","journal-title":"Brain"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1177\/1352458506070629","article-title":"Retinal Ganglion Cell Loss Induced by Acute Optic Neuritis in a Relapsing Model of Multiple Sclerosis","volume":"12","author":"Shindler","year":"2006","journal-title":"Mult Scler"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(83)90822-3","article-title":"Immunocytochemical Staining for Glial Fibrillary Acidic Protein and the Metabolism of Cytoskeletal Proteins in Experimental Allergic Encephalomyelitis","volume":"264","author":"Smith","year":"1983","journal-title":"Brain Res"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-021-01049-8","article-title":"The GFAP Monoclonal Antibody GA-5 Identifies Astrocyte Remodeling and Glio-Vascular Uncoupling During the Evolution of EAE","author":"Halder","year":"2021","journal-title":"Cell Mol Neurobiol"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-010-5863-2","article-title":"Glial Fibrillary Acidic Protein: A Potential Biomarker for Progression in Multiple Sclerosis","volume":"258","author":"Axelsson","year":"2011","journal-title":"J Neurol"},{"key":"B58","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1111\/bpa.12099","article-title":"The Pathology of an Autoimmune Astrocytopathy: Lessons Learned From Neuromyelitis Optica","volume":"24","author":"Lucchinetti","year":"2014","journal-title":"Brain Pathol"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23727","article-title":"Glia of the Human Retina","volume":"68","author":"Reichenbach","year":"2020","journal-title":"Glia"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1159\/000119879","article-title":"Optic Nerve Degeneration in Experimental Autoimmune Encephalomyelitis","volume":"40","author":"Guy","year":"2008","journal-title":"Ophthalmic Res"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-022516-034406","article-title":"Microglia in Physiology and Disease","volume":"79","author":"Wolf","year":"2017","journal-title":"Annu Rev Physiol"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-019-0253-6","article-title":"When Encephalitogenic T Cells Collaborate With Microglia in Multiple Sclerosis","volume":"15","author":"Dong","year":"2019","journal-title":"Nat Rev Neurol"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-019-0035-2","article-title":"Progressive Multiple Sclerosis: From Pathophysiology to Therapeutic Strategies","volume":"18","author":"Faissner","year":"2019","journal-title":"Nat Rev Drug Discov"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1172\/JCI134816","article-title":"Astrocyte-Microglia Interaction Drives Evolving Neuromyelitis Optica Lesion","volume":"130","author":"Chen","year":"2020","journal-title":"J Clin Invest"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2020.00269","article-title":"Dynamic Responses of Microglia in Animal Models of Multiple Sclerosis","volume":"14","author":"Plastini","year":"2020","journal-title":"Front Cell Neurosci"},{"key":"B66","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1186\/1742-2094-8-184","article-title":"Complement Activating Antibodies to Myelin Oligodendrocyte Glycoprotein in Neuromyelitis Optica and Related Disorders","volume":"8","author":"Mader","year":"2011","journal-title":"J Neuroinflamm"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0901-04.2004","article-title":"Absence of C1q Leads to Less Neuropathology in Transgenic Mouse Models of Alzheimer's Disease","volume":"24","author":"Fonseca","year":"2004","journal-title":"J\u00a0Neurosci"},{"key":"B68","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1186\/s12974-017-0814-9","article-title":"Cell-Specific Deletion of C1qa Identifies Microglia as the Dominant Source of C1q in Mouse Brain","volume":"14","author":"Fonseca","year":"2017","journal-title":"J Neuroinflamm"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2020.03.004","article-title":"Complement-Dependent Synapse Loss and Microgliosis in a Mouse Model of Multiple Sclerosis","volume":"87","author":"Hammond","year":"2020","journal-title":"Brain Behav Immun"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00362","article-title":"Therapeutic Inhibition of the Complement System in Diseases of the Central Nervous System","volume":"10","author":"Carpanini","year":"2019","journal-title":"Front Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.759389\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,24]],"date-time":"2022-01-24T05:22:43Z","timestamp":1643001763000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.759389\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,24]]},"references-count":70,"alternative-id":["10.3389\/fimmu.2021.759389"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2021.759389","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,24]]},"article-number":"759389"}}