MOG35 - 55-induced EAE model of optic nerve inflammation compared to MS, MOGAD and NMOSD related subtypes of human optic neuritis.

Abstract

Optic neuritis (ON), or inflammation of the optic nerve, is a common presenting symptom of demyelinating neuroinflammatory conditions that result in significant, subacute vision loss. Given its association with visual impairment and varying extent of visual recovery, ON has been recognized as a significant health burden with a need for new therapeutic strategies to improve long-term visual outcomes. Among the resources utilized to study ON, animal models have emerged as powerful tools to examine the underlying pathophysiology and the effectiveness of proposed therapies. In the current review, we discuss the functional and structural phenotypes related to ON in currently used mouse models, and summarize how the pathophysiology and visual phenotype of the myelin oligodendrocyte glycoprotein 35-55 (MOG_35 - 55) experimental autoimmune encephalomyelitis (EAE) mouse model recapitulates clinical features of multiple sclerosis (MS), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and neuromyelitis optica spectrum disorder (NMOSD). The location of ON and the amount of visual recovery in the EAE model most closely resembles MS and NMOSD. However, we propose that the MOG_35 - 55-induced EAE model of ON is primarily a MOGAD model given its similarity in pathophysiology, spinal cord demyelination pattern, and the degree of vision loss, retinal nerve fiber layer (RNFL) swelling, and disc edema. Overall, the MOG_35 - 55-induced EAE animal model demonstrates overlapping features of autoimmune demyelinating conditions and serves as a comprehensive tool to further our understanding of visual impairment in all three conditions.