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Updated: Jun 30, 2026
Two-photon Imaging of Cellular Dynamics in the Mouse Spinal Cord
Published on: February 22, 2015
Alleviation of extensive visual pathway dysfunction by a remyelinating drug in a chronic mouse model of multiple
Maria T Sekyi1,2, Kelli Lauderdale1, Kelley C Atkinson1
1Division of Biomedical Sciences, Riverside School of Medicine, University of California, Riverside, CA, USA.
Abstract:
Visual deficits are among the most prevalent symptoms in patients with multiple sclerosis (MS). To understand deficits in the visual pathway during MS and potential treatment effects, we used experimental autoimmune encephalomyelitis (EAE), the most commonly used animal model of MS. The afferent visual pathway was assessed in vivo using optical coherence tomography (OCT), electroretinography (ERG), and visually evoked cortical potentials (VEPs). Inflammation, demyelination, and neurodegeneration were examined by immunohistochemistry ex vivo. In addition, an immunomodulatory, remyelinating agent, the estrogen receptor β ligand chloroindazole (IndCl), was tested for its therapeutic potential in the visual pathway. EAE produced functional deficits in visual system electrophysiology, including suppression of ERG and VEP waveform amplitudes and increased signal latencies. Therapeutic IndCl rescued overall visual system latency by VEP but had little impact on amplitude or ERG findings relative to vehicle. Faster VEP conduction in IndCl-treated mice was associated with enhanced myelin basic protein signal in all visual system structures examined. IndCl preserved retinal ganglion cells (RGCs) and oligodendrocyte density in the prechiasmatic white matter, but similar retinal nerve fiber layer thinning by OCT was noted in vehicle and IndCl-treated mice. Although IndCl differentially attenuated leukocyte and astrocyte staining signal throughout the structures analyzed, axolemmal varicosities were observed in all visual fiber tracts of mice with EAE irrespective of treatment, suggesting impaired axonal energy homeostasis. These data support incomplete functional recovery of VEP amplitude with IndCl, as fiber tracts displayed persistent axon pathology despite remyelination-induced decreases in latencies, evidenced by reduced optic nerve g-ratio in IndCl-treated mice. Although additional studies are required, these findings demonstrate the dynamics of visual pathway dysfunction and disability during EAE, along with the importance of early treatment to mitigate EAE-induced axon damage.
Insights
Multiple sclerosis (MS) causes visual deficits. A study using an MS animal model found that chloroindazole (IndCl) improved visual pathway speed but did not fully restore function, highlighting persistent axon damage.
Area of Science:
- Neuroscience
- Immunology
- Ophthalmology
Background:
- Visual deficits are common in multiple sclerosis (MS).
- Experimental autoimmune encephalomyelitis (EAE) is a key animal model for studying MS.
- The visual pathway's vulnerability in MS necessitates understanding disease mechanisms and therapeutic interventions.
Purpose of the Study:
- To investigate visual pathway dysfunction in EAE, an MS model.
- To evaluate the therapeutic potential of chloroindazole (IndCl), an estrogen receptor β ligand, on visual pathway integrity and function.
- To assess the impact of IndCl on inflammation, demyelination, neurodegeneration, and axonal health.
Main Methods:
- In vivo assessment of the afferent visual pathway using optical coherence tomography (OCT), electroretinography (ERG), and visually evoked cortical potentials (VEPs).
- Ex vivo analysis of inflammation, demyelination, and neurodegeneration via immunohistochemistry.
- Treatment with IndCl in EAE mice to evaluate its therapeutic effects.
Main Results:
- EAE induced significant visual electrophysiological deficits, including reduced ERG and VEP amplitudes and increased latencies.
- IndCl treatment improved VEP conduction speed, associated with increased myelin basic protein, and preserved retinal ganglion cells and oligodendrocytes.
- Despite remyelination and latency improvements, IndCl did not fully restore VEP amplitudes, and persistent axonal pathology (varicosities) was observed, indicating impaired energy homeostasis.
Conclusions:
- IndCl demonstrates therapeutic potential in the MS visual pathway by reducing latency and preserving neural elements.
- However, functional recovery remains incomplete, with persistent axon damage suggesting limitations in current therapeutic strategies.
- Early intervention is crucial to mitigate axon damage and improve outcomes in MS-related visual impairment.
