Functional and structural visual pathway alterations in experimental autoimmune encephalomyelitis mouse model
Abstract
Experimental autoimmune encephalomyelitis (EAE) is a common animal model to study multiple sclerosis (MS), an autoimmune and demyelinating disease of the central nervous system. In 30% of MS patients clinical presentation starts with optic neuritis (ON). C57BL/6 mice (n=20) were immunized with myelin oligodendrocyte glycoprotein peptide exhibited a chronic disease course, together with ON. We aimed at investigating ON with two follow up studies, using non-invasive methods: visual evoked potentials (VEPs), photopic electroretinograms (pERG), optic coherence tomography (OCT). At the end, optic nerve histology were performed to confirm electrophysiological results. Moreover clinical score was measured daily. In the short follow up EAE mice showed significant VEP latency increased confirmed by demyelination. Moreover, optic nerve histology showed significant axonal loss and microglia/macrophage cells already at 7 dpi. However, any structural and functional retinal alterations were detected. In the second follow up study clinical motor onset was detect at 11 dpi. Eyes of EAE mice showed significant VEP latency increased from 7 to 37 dpi, while amplitude decreased from 19 dpi until the end of the experiment. Regarding retina alterations both PhNR and b wave amplitude decreased from 15 to 37 dpi. Both electrophysiological recording, VEP and pERG, were confirmed by optic nerve histology and OCT, respectively. Thus interestingly, EAE mice before clinical onset showed a dysfunction focused only in the optic nerve. To conclude, our non-invasive methods can be applied to characterize the visual pathway alterations at very early time point in order to develop more effective treatments.