Journal article
Correlation of Visual System Biomarkers With Motor Deficits in Experimental Autoimmune Encephalomyelitis-Optic Neuritis
Translational vision science & technology, Vol.13(8), pp.1-11
08/01/2024
DOI: 10.1167/tvst.13.8.1
PMCID: PMC11305423
PMID: 39087931
Abstract
Experimental autoimmune encephalomyelitis (EAE) scoring, the most commonly used primary outcome metric for an in vivo model of multiple sclerosis (MS), is highly variable and subjective. Here we explored the use of visual biomarkers in EAE as more objective and clinically relevant primary outcomes.PurposeExperimental autoimmune encephalomyelitis (EAE) scoring, the most commonly used primary outcome metric for an in vivo model of multiple sclerosis (MS), is highly variable and subjective. Here we explored the use of visual biomarkers in EAE as more objective and clinically relevant primary outcomes.Motor impairment in myelin oligodendrocyte glycoprotein-immunized C57BL/6J mice was quantified using a five-point EAE grading scale. Pattern electroretinography (pERG) and retinal ganglion cell/inner plexiform layer (RGC/IPL) complex thickness were measured 60 days after induction. Optic nerve histopathology was analyzed at endpoint.MethodsMotor impairment in myelin oligodendrocyte glycoprotein-immunized C57BL/6J mice was quantified using a five-point EAE grading scale. Pattern electroretinography (pERG) and retinal ganglion cell/inner plexiform layer (RGC/IPL) complex thickness were measured 60 days after induction. Optic nerve histopathology was analyzed at endpoint.EAE mice displayed motor impairments ranging from mild to severe. Significant correlations were seen between pERG amplitude and last EAE score, mean EAE score, and cumulative EAE score. Optical coherence tomography (OCT) analysis demonstrated a significant correlation between thinning of the RGC/IPL complex and both EAE score and pERG amplitude. Optic nerve histopathology showed significant correlations between demyelination and cumulative EAE score, pERG amplitude, and RGC/IPL complex thickness, as well as between immune cell infiltration and cumulative EAE score, pERG amplitude, and RGC/IPL complex thickness in EAE mice.ResultsEAE mice displayed motor impairments ranging from mild to severe. Significant correlations were seen between pERG amplitude and last EAE score, mean EAE score, and cumulative EAE score. Optical coherence tomography (OCT) analysis demonstrated a significant correlation between thinning of the RGC/IPL complex and both EAE score and pERG amplitude. Optic nerve histopathology showed significant correlations between demyelination and cumulative EAE score, pERG amplitude, and RGC/IPL complex thickness, as well as between immune cell infiltration and cumulative EAE score, pERG amplitude, and RGC/IPL complex thickness in EAE mice.Unlike EAE scoring, pERG and OCT show direct measurement of retinal structure and function. Therefore we conclude that visual outcomes are well suited as a direct assessment of optic nerve involvement in this EAE model of MS while also being indicative of motor impairment.ConclusionsUnlike EAE scoring, pERG and OCT show direct measurement of retinal structure and function. Therefore we conclude that visual outcomes are well suited as a direct assessment of optic nerve involvement in this EAE model of MS while also being indicative of motor impairment.Standardizing directly translatable measurements as primary outcome parameters in the murine EAE model could lead to more rapid and relevant testing of new therapeutic approaches for mitigating MS.Translational RelevanceStandardizing directly translatable measurements as primary outcome parameters in the murine EAE model could lead to more rapid and relevant testing of new therapeutic approaches for mitigating MS.
Details
- Title: Subtitle
- Correlation of Visual System Biomarkers With Motor Deficits in Experimental Autoimmune Encephalomyelitis-Optic Neuritis
- Creators
- Benjamin W Elwood - University of IowaCheyanne R Godwin - University of IowaJeffrey J Anders - University of IowaRandy H Kardon - University of IowaOliver W Gramlich - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Translational vision science & technology, Vol.13(8), pp.1-11
- Publisher
- ASSOC RESEARCH VISION OPHTHALMOLOGY INC
- DOI
- 10.1167/tvst.13.8.1
- PMID
- 39087931
- PMCID
- PMC11305423
- ISSN
- 2164-2591
- eISSN
- 2164-2591
- Grant note
- United States (U.S.) Department of Veterans Affairs Rehabilitation Research and Development Service: 1I01RX002978-01, 1I50RX003002-01
Supported by Merit Grant 1I01RX002978-01 and Center Grant 1I50RX003002-01 from the United States (U.S.) Department of Veterans Affairs Rehabilitation Research and Development Service.
- Language
- English
- Date published
- 08/01/2024
- Academic Unit
- Iowa Neuroscience Institute; Neuroscience and Pharmacology; Ophthalmology and Visual Sciences
- Record Identifier
- 9984693979102771
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