Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 116, Issue 52, Pages 27074-27083Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1906358116
Keywords
demyelination; remyelination; optic nerve; VEP; animal model
Categories
Funding
- National Multiple Sclerosis Society (NMSS) [RG 1501-02876]
- Myelin Project
- NIH [K08 EY018609, R01 EY027396]
- Core Grant for Vision Research [P30 EY016665]
- National Glaucoma Research Award from BrightFocus Foundation [G2016129]
- University of WisconsinMadison Office of the Vice Chancellor for Research and Graduate Education
- Wisconsin Alumni Research Foundation
- Research to Prevent Blindness
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Multiple sclerosis (MS) is a common cause of neurologic disease in young adults that is primarily treated with disease-modifying therapies which target the immune and inflammatory responses. Promotion of remyelination has opened a new therapeutic avenue, but how best to determine efficacy of remyelinating drugs remains unresolved. Although prolongation and then shortening of visual evoked potential (VEP) latencies in optic neuritis in MS may identify demyelination and remyelination, this has not been directly confirmed. We recorded VEPs in a model in which there is complete demyelination of the optic nerve, with subsequent remyelination. We examined the optic nerves microscopically during active disease and recovery, and quantitated both demyelination and remyelination along the length of the nerves. Latencies of the main positive component of the control VEP demonstrated around 2-fold prolongation during active disease. VEP waveforms were nonrecordable in a few subjects or exhibited a broadened profile which precluded peak identification. As animals recovered neurologically, the VEP latencies decreased in association with complete remyelination of the optic nerve but remained prolonged relative to controls. Thus, it has been directly confirmed that VEP latencies reflect the myelin status of the optic nerve and will provide a surrogate marker in future remyelination clinical trials.
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