Correlation of visual system biomarkers with motor-sensory deficits in experimental autoimmune encephalomyelitis-optic neuritis

Abstract

Abstract Experimental autoimmune encephalomyelitis (EAE) scoring, the most commonly used primary outcome metric for an in vivo model of multiple sclerosis (MS), is highly variable and subjective. Here, we explored the use of visual biomarkers in EAE as more objective and clinically relevant primary outcomes. Motor-sensory impairment in myelin oligodendrocyte glycoprotein-immunized C57BL/6J mice was quantified using a 5-point EAE scoring scheme. Pattern electroretinography (pERG) and retinal ganglion cell / inner plexiform layer (RGC/IPL) complex thickness were measured 60 days after induction. Optic nerve histopathology was analyzed at endpoint. EAE mice displayed motor-sensory impairments ranging from mild to severe. Significant correlations were seen between pERG amplitude and last EAE score, mean EAE score, and cumulative EAE score. Optical coherence tomography (OCT) analysis demonstrated a significant correlation between thinning of the RGC/IPL complex and both the cumulative EAE score and the pERG amplitude. Optic nerve histopathology showed significant correlations between demyelination and cumulative EAE score, pERG amplitude, and RGC/IPL complex thickness, as well as between immune cell infiltration and cumulative EAE score, pERG amplitude, and RGC/IPL complex thickness in EAE mice. Unlike EAE scoring, pERG and OCT show direct measurement of retinal structure and function. Therefore, we conclude that visual outcomes are well-suited as a direct assessment of optic nerve involvement in this EAE model of MS, while also being indicative of motor-sensory impairment. Standardizing parameters could lead to a more rapid and robust model for testing new therapeutic approaches for mitigating MS by utilizing deep learning and artificial intelligence.