Temporal progression of axonal degeneration in the visual system in experimental autoimmune encephalomyelitis: Insights from high-resolution neuropathology

Abstract

Multiple sclerosis (MS) is characterized by inflammation, demyelination, and axonal degeneration in the CNS, leading to progressive neurological disability is generally regarded as an autoimmune disorder. Visual impairment, a frequent symptom, results from damage to retinal ganglion cells (RGCs) and their axons in the anterior visual pathway. Using the experimental autoimmune encephalomyelitis (EAE) model in mice, we used several methods, including high-resolution neuropathology with a novel immunohistochemical technique on ultrathin sections, to characterize axonal pathology and demyelination, terminal disruption, perikaryal degeneration, and visual acuity. Electron microscopy demonstrated early axonopathy and myelin splitting, progressing to severe degradation of axons and myelin sheaths. Severe transport deficits in the optic nerve correlated with loss of labeling of retinocollicular terminals. Visual acuity, assessed by optomotor response (OMR), significantly declined at peak stage in the EAE group and remained impaired throughout the course of disease. These findings reveal the temporal progression of neurodegeneration with a dying-back pattern in EAE and emphasize the importance of early intervention to prevent permanent damage. They also point to the importance of novel methods in generating new insights in classical models of neurological disease.

Keywords: axonal degeneration; experimental autoimmune encephalomyelitis (EAE); inflammation; multiple sclerosis (MS); retinal ganglion cells (RGCs); visual pathway.