Functional evolution of visual involvement in experimental autoimmune encephalomyelitis
Silvia Marenna1, Su-Chun Huang1, Valerio Castoldi1
1Experimental Neurophysiology Unit, Institute of Experimental Neurology-INSPE, IRCCS San Raffaele Hospital, Milan, Italy.
Background:
Experimental autoimmune encephalomyelitis (EAE) is a common animal model of multiple sclerosis (MS). C57BL/6 mice immunized with myelin oligodendrocyte glycoprotein exhibit chronic disease course, together with optic neuritis, consisting of demyelination/axonal loss of the optic nerve.
Objectives:
To characterize functional and structural visual damages in two different phases of EAE: pre- and post-motor onset.
Methods:
Visual alterations were detected with Visual Evoked Potential (VEP), Electroretinogram (ERG) and Optical Coherence Tomography (OCT). Optic nerve histology was performed at 7 (pre-motor onset) or 37 (post-motor onset) days post-immunization (dpi).
Results:
At 7 dpi, optic nerve inflammation was similar in EAE eyes with and without VEP latency delay. Demyelination was detected in EAE eyes with latency delay (p < 0.0001), while axonal loss (p < 0.0001) and ERG b-wave amplitude (p = 0.004) were decreased in EAE eyes without latency delay compared to Healthy controls. At 37 dpi, functional and structural optic nerve damage were comparable between EAE groups, while a decrease of ERG amplitude and NGCC thickness were found in EAE eyes with VEP latency delay detected post-motor onset.
Conclusions:
Thanks to non-invasive methods, we studied the visual system in a MS model, which could be useful for developing specific therapeutic strategies to target different disease phases.
Insights
This study investigated visual system damage in a multiple sclerosis (MS) mouse model. Early optic nerve demyelination and later axonal loss correlate with visual dysfunction, aiding therapeutic development.
Area of Science:
- Neuroscience
- Ophthalmology
- Immunology
Background:
- Experimental autoimmune encephalomyelitis (EAE) serves as a key animal model for multiple sclerosis (MS).
- Mice immunized with myelin oligodendrocyte glycoprotein develop chronic EAE, featuring optic neuritis, demyelination, and axonal loss in the optic nerve.
Purpose of the Study:
- To comprehensively characterize both functional and structural visual impairments during distinct phases of EAE: pre-motor and post-motor onset.
- To correlate visual system changes with disease progression in an MS model.
Main Methods:
- Utilized non-invasive techniques: Visual Evoked Potential (VEP), Electroretinogram (ERG), and Optical Coherence Tomography (OCT) to assess visual function and structure.
- Performed optic nerve histology at 7 days post-immunization (dpi) for pre-motor onset and 37 dpi for post-motor onset EAE.
Main Results:
- Pre-motor onset (7 dpi): Demyelination linked to VEP latency delay; axonal loss and reduced ERG b-wave amplitude observed in eyes without VEP delay.
- Post-motor onset (37 dpi): Comparable functional and structural optic nerve damage across EAE groups.
- Post-motor onset EAE with VEP latency delay showed decreased ERG amplitude and Normalized Ganglion Cell Complex (NGCC) thickness.
Conclusions:
- Non-invasive methods effectively evaluated the visual system in an MS model.
- Findings provide insights into distinct visual system damage patterns across EAE phases.
- This research can inform the development of targeted therapeutic strategies for different stages of MS.
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