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

• Published in: Journal of neuroscience methods 2007-11, Vol.166 (2), p.217-228
• Main Authors: Stokely, Martha E., Bhat, Manzoor A., Koulen, Peter
• Format: Article
• Language: English
• Subjects: Amyloid beta-Protein Precursor - metabolism; Animals; Autoimmune optic neuritis; Axon pathology; Axons - metabolism; Axons - pathology; Cell Adhesion Molecules, Neuronal - metabolism; Disease Models, Animal; Endothelin-1 - metabolism; Experimental methods; Female; Flow Cytometry - methods; Gene Expression Regulation - drug effects; Gene Expression Regulation - physiology; Glial Fibrillary Acidic Protein - metabolism; Glycoproteins; Mast Cells - metabolism; Mast Cells - pathology; Multiple sclerosis; Myelin-Oligodendrocyte Glycoprotein; Optic Neuritis - chemically induced; Optic Neuritis - metabolism; Optic Neuritis - pathology; Peptide Fragments; Rats
• ISSN: 0165-0270; 1872-678X
• DOI: 10.1016/j.jneumeth.2007.07.010

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.