A longitudinal study was conducted combining optical coherence tomography (OCT) retinal imaging and immunohistochemical analyses of retinal and optic nerve tissue in experimental autoimmune encephalomyelitis (EAE).

The exact mechanisms and temporal sequence of neurodegeneration in multiple sclerosis are still unresolved. The visual pathway can serve as a prototypic model of neurodegeneration in EAE, a mouse model of multiple sclerosis.

Inner retinal layer (IRL) thickness was measured in 30 EAE and 14 healthy C57BL/6J mice using OCT. Distribution of marker proteins was assessed using immunofluorescence and mRNA levels were assayed with real-time PCR. Histological morphology was evaluated with electron microscopy.

Signs of inflammatory edema 11 days post immunisation (dpi) coincided with IRL thickening, while neuro-axonal degeneration throughout the disease course contributed to IRL thinning observed after 20 dpi. Early retinal pathology, including axonal transport impairment, was observed prior to cellular infiltration (i.e. T-cells) in the optic nerve 11 dpi. However, the consequences of early retinal damage on OCT-derived measurements were offset by the initial inflammatory edema. Microgliosis and astrocytosis was detected in the retina prior to optic neuritis and persisted until 33 dpi. Müller cell reactivity (i.e. aquaporin-4 and glutamine synthetase decrease) occurred after 11 dpi in the IRL. Severe neuro-axonal degeneration was observed in the optic nerve and retina until 33 dpi.

Initial signs of retinal pathology subsequent to early glial activity, suggests a need for prophylactic treatment of optic neuritis. Future studies should explore Müller cell reactivity and its potentially neuroprotective role. Although, retrograde degeneration likely promoted the majority of observed IRL damage following optic neuritis, primary pathology - possibly due to gliosis – also contributed to IRL thinning. These results add morphological substrate to our OCT findings. The extent and rapid onset of axonal and neuronal damage in this model appears relevant for testing interventions scaled to multiple sclerosis.