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It frequently manifests as the initial symptom and a recurrent syndrome in patients with myelin oligodendrocyte glycoprotein antibody\u2010associated disease (MOGAD), neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS). While the diagnosis of ON is relatively straightforward, predicting relapses and managing the disease remain significant challenges. The myelination of retinal ganglion cell axons is essential for the efficient and accurate transmission of signals between optic neurons. Oligodendrocytes, specialized glial cells responsible for myelination, engage in metabolic interactions with neurons. Demyelination and inflammation of the optic nerve locally release a variety of metabolites and inflammatory factors within this unique anatomical region. Cerebrospinal fluid (CSF), in close proximity to ON lesions, is a critical source for identifying metabolic and inflammatory biomarkers that are essential for tracking disease activity and guiding therapeutic decisions. This comprehensive review examines the structure, myelination and demyelination of the optic nerve, as well as the immunopathological mechanisms underlying ON. It also explores changes in CSF constituents, including pleocytosis, antibodies, cytokines, proteins, metabolites and extracellular vesicles. Special emphasis is placed on elucidating the pathological contributions of metabolites in MOGAD, MS and NMOSD. By advancing our understanding of these mechanisms, this review elucidates the potential predictive roles of CSF constituents in acute attacks and relapses of optic neuritis.<\/jats:p>","DOI":"10.1111\/imcb.70059","type":"journal-article","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T22:44:41Z","timestamp":1759185881000},"page":"916-937","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Immunopathology of optic neuritis and cerebrospinal fluid biomarkers for acute attack and relapse prediction"],"prefix":"10.1111","volume":"103","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5666-9497","authenticated-orcid":false,"given":"Rong","family":"Jin","sequence":"first","affiliation":[{"name":"Beijing Life Science Academy  Beijing China"},{"name":"Department of Immunology, School of Basic Medical Sciences Peking University  Beijing China"},{"name":"NHC Key Laboratory of Medical Immunology Peking University  Beijing China"},{"name":"Medicine Innovation Center for Fundamental Research on Major Immunology\u2010related Diseases Peking University  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shihao","family":"Sun","sequence":"additional","affiliation":[{"name":"Beijing Life Science Academy  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangyi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Beijing Tongren Hospital Capital Medical University  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Basic Medical Sciences Peking University  Beijing China"},{"name":"NHC Key Laboratory of Medical Immunology Peking University  Beijing China"},{"name":"Medicine Innovation Center for Fundamental Research on Major Immunology\u2010related Diseases Peking 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