Immunopathology of the optic nerve in multiple sclerosis

Optic neuritis, a primary clinical manifestation commonly observed in multiple sclerosis (MS), is a major factor leading to permanent loss of vision. Despite decreased vision (optic neuritis), diplopia, and nystagmus, the immunopathology of the optic nerve in MS is unclear. Here, we have characterized the optic nerve pathology in a large cohort of MS cases (n = 154), focusing on the immune responses in a sub-cohort of MS (n = 30) and control (n = 6) cases. Immunohistochemistry was used to characterize the myeloid (HLA-DR, CD68, Iba1, TMEM119, and P2RY12) and adaptive immune cells (CD4, CD8, and CD138) in the parenchyma, perivascular spaces, and meninges in optic nerve tissues from MS and control cases. Of the 154 MS cases, 122 (79%) reported visual problems; of which, 99 (81%) optic nerves showed evidence of damage. Of the 31 cases with no visual disturbances, 19 (61%) showed evidence of pathology. A pattern of myeloid cell activity and demyelination in the optic nerve was similar to white matter lesions in the brain and spinal cord. In the optic nerves, adaptive immune cells were more abundant in the meninges close to active and chronic active lesions, and significantly higher compared with the parenchyma. Similar to brain tissues in this Dutch cohort, B-cell follicles in the meninges were absent. Our study reveals that optic nerve pathology is a frequent event in MS and may occur in the absence of clinical symptoms.