AUTHOR=He Yuhong , Guo Kai , Xin Jifu 

TITLE=Complement updates in optic neuritis

JOURNAL=Frontiers in Neurology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2025.1566771

DOI=10.3389/fneur.2025.1566771

ISSN=1664-2295

ABSTRACT=Optic neuritis (ON) is an inflammatory condition of the optic nerve associated with demyelinating diseases like multiple sclerosis, neuromyelitis optica spectrum disorder, and myelin oligodendrocyte glycoprotein antibody-associated disease. The complement system is crucial in ON pathogenesis, driving blood-optic nerve barrier disruption, inflammation, and tissue damage. This review explores the complement activation pathways—classical, alternative, and lectin—and their roles in ON progression. Key proteins such as C3, C5, and terminal pathway components are highlighted as central to disease mechanisms. Recent advances in complement-targeted therapies, including C1q blockers, C3 and C5 inhibitors, show promising results in clinical and preclinical studies. Novel therapies, like anaphylatoxin receptor blockers and recombinant factor H, expand the treatment landscape, while plasma exchange remains vital for severe, corticosteroid-resistant cases. Challenges remain, such as ON heterogeneity, the long-term safety of complement inhibition, and the need for personalized approaches. Future studies should focus on unraveling complement-mediated mechanisms, identifying biomarkers, and refining therapeutic strategies. This review highlights the critical role of complement in ON and the latest therapeutic advances to improve patient outcomes.