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Updated: Jul 12, 2026
Bioluminescence and Near-infrared Imaging of Optic Neuritis and Brain Inflammation in the EAE Model of Multiple Sclerosis in Mice
Published on: March 1, 2017
Microfluorimetry defines early axonal damage in a rat model of optic neuritis: a novel method targeting early CNS
Martha E Stokely1, Manzoor A Bhat, Peter Koulen
1Department of Pharmacology and Neuroscience, University of North Texas Health Science Center at Fort Worth, Fort Worth, TX 76107, USA.
Abstract:
Autoimmune optic neuritis is a common early manifestation of multiple sclerosis (MS), yet early therapeutic interventions for MS often have high ocular toxicity associated with increased risks for glaucoma, cataract, or retinopathy. This need to discover better early treatment options prompted our development of a sensitive and reliable means to quantify the broad range of pathologies that potentially develop very early in autoimmune optic neuritis. Tissue microfluorimetry was used to measure seven established markers for human MS pathology in normal and autoimmune optic nerves 13 days after antigen exposure, in a Brown Norway rat model of myelin oligodendrocyte glycoprotein (MOG) peptide (35-55)-induced autoimmune optic neuritis. Optic neuritis rats demonstrated early and significant pathologic changes in five established indices for neuroinflammation, immune infiltration, and demyelination that accurately modeled pathologies characteristic of MS. Two indices of MS-like axon damage advanced significantly within 13 days of antigen exposure. Fluorimetrically measured immunoreactivity (-ir) was significantly decreased for paranodin (PN, the requisite axonal paranodal junction protein) and significantly increased for amyloid precursor protein (APP), indicating loss of paranodal junctions and impaired fast axonal transport, respectively. Measurements showing decreased PN-ir with increased APP-ir quantitatively defined a pattern of early axonal damage in autoimmune optic neuritis.
Insights
Early autoimmune optic neuritis, a multiple sclerosis precursor, shows significant axonal damage. New methods quantify neuroinflammation, demyelination, and axonal injury, aiding the search for safer treatments.
Area of Science:
- Neuroimmunology
- Ophthalmology
- Neuropathology
Background:
- Autoimmune optic neuritis is an early sign of multiple sclerosis (MS).
- Current MS treatments carry ocular toxicity risks, necessitating better early interventions.
- Early detection of pathologies in optic neuritis is crucial for managing MS.
Purpose of the Study:
- To develop a sensitive method for quantifying early pathologies in autoimmune optic neuritis.
- To model MS-like pathologies in an animal model.
- To identify early markers of axonal damage.
Main Methods:
- Utilized a Brown Norway rat model of experimental autoimmune optic neuritis induced by myelin oligodendrocyte glycoprotein (MOG) peptide (35-55).
- Employed tissue microfluorimetry to measure seven established markers of human MS pathology.
- Assessed optic nerves 13 days post-antigen exposure.
Main Results:
- Rats with optic neuritis showed significant neuroinflammation, immune infiltration, and demyelination.
- Early axonal damage was identified, characterized by decreased paranodin immunoreactivity (PN-ir) and increased amyloid precursor protein immunoreactivity (APP-ir).
- These changes indicate loss of paranodal junctions and impaired fast axonal transport.
Conclusions:
- The developed method reliably quantifies early pathologies in autoimmune optic neuritis.
- The findings provide a quantitative pattern of early axonal damage relevant to MS.
- This research supports the development of safer, targeted early MS therapies.
