Abstract
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) featuring numerous neuropathologies, including optic neuritis (ON) in some patients. However, the molecular mechanisms of ON remain unknown. Galectins, β-galactoside-binding lectins, are involved in various pathophysiological processes. We previously showed that galectin-3 (gal-3) is associated with the pathogenesis of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. In the current study, we investigated the expression of gal-3 in the visual pathway in EAE mice to clarify its role in the pathogenesis of ON. Immunohistochemical analysis revealed upregulation of gal-3 in the visual pathway of the EAE mice during the peak stage of the disease, compared with naïve and EAE mice during the chronic stage. Gal-3 was detected mainly in microglia/macrophages and astrocytes in the visual pathway in EAE mice. In addition, gal-3(+)/Iba-1(+) cells, identified as phagocytic by immunostaining for cathepsin D, accumulated in demyelinating lesions in the visual pathway during the peak disease stage of EAE. Moreover, NLRP3 expression was detected in most gal-3(+)/Iba-1(+) cells. These results strongly suggest that gal-3 regulates NLRP3 signaling in microglia/macrophages and neuroinflammatory demyelination in ON. In astrocytes, gal-3 was expressed from the peak to the chronic disease stages. Taken together, our findings suggest a critical role of gal-3 in the pathogenesis of ON. Thus, gal-3 in glial cells may serve as a potential therapeutic target for ON.