Microfluorimetry defines early axonal damage in a rat model of optic neuritis: A novel method targeting early CNS autoimmunity

Martha E. Stokely, Manzoor A. Bhat, Peter Koulen

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)217-228
Number of pages12
JournalJournal of Neuroscience Methods
Volume166
Issue number2
DOIs
StatePublished - Nov 30 2007
Externally publishedYes

Keywords

  • Autoimmune optic neuritis
  • Axon pathology
  • Experimental methods
  • Multiple sclerosis

ASJC Scopus subject areas

  • Neuroscience(all)

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