Posterior Visual Pathway Dysfunction in Two Animal Models of Multiple Sclerosis: Understanding Pathology for Regeneration and Repair
- Author(s): Sekyi, Maria Theresa
- Advisor(s): Tiwari-Woodruff, Seema K
- et al.
Visual dysfunction is pronounced in multiple sclerosis (MS) an autoimmune, demyelinating, neurodegenerative disease. To understand deficits in the visual pathway during MS a broader understanding of pathology and function across the visual system is needed. Here, afferent visual pathway pathology is first assessed in the most commonly used animal model of MS, experimental autoimmune encephalomyelitis (EAE). A remyelinating agent is then assessed for its therapeutic efficacy in attenuating visual pathway dysfunction. Although treatment results in robust remyelination across the visual pathway, severe axon damage remains and functional loss is not attenuated possibly due to treatment timing. The time course of posterior visual pathway pathology is then assessed in EAE in order to identify an ideal therapeutic window for remyelination, prior to irreversible axon damage and functional loss. The therapeutic window, corresponding to a period of significant demyelination but minimal axon damage, is found to occur after EAE onset, but prior to peak clinical disease. Visual pathway pathology is then assayed in another animal model for MS, the cuprizone (CPZ) demyelination model, which induces CNS demyelination absent of a peripherally mediated immune response. Similar to EAE, visual pathway demyelination is a prominent feature of CPZ pathology, however axon damage and severe functional deficits are not. These results reveal a significant role of inflammatory demyelination in causing visual pathway neurodegeneration in EAE as compared to minimal axon damage with CPZ demyelination, mimicking diverse pathology observed in MS patients.