TY - JOUR
T1 - Microfluorimetry defines early axonal damage in a rat model of optic neuritis
T2 - A novel method targeting early CNS autoimmunity
AU - Stokely, Martha E.
AU - Bhat, Manzoor A.
AU - Koulen, Peter
N1 - Funding Information:
The authors would like to thank Elaine Gregg, and Nataliya Rybalchenko for their expert technical assistance. This work was supported in part by NIH grants EY14227, AG22550, AG10485 (PK), AT03605 (MS), and Texas ARP grant # 000130-0007-2006 (PK).
PY - 2007/11/30
Y1 - 2007/11/30
N2 - 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.
AB - 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.
KW - Autoimmune optic neuritis
KW - Axon pathology
KW - Experimental methods
KW - Multiple sclerosis
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U2 - 10.1016/j.jneumeth.2007.07.010
DO - 10.1016/j.jneumeth.2007.07.010
M3 - Article
C2 - 17719649
AN - SCOPUS:35648994881
SN - 0165-0270
VL - 166
SP - 217
EP - 228
JO - Journal of Neuroscience Methods
JF - Journal of Neuroscience Methods
IS - 2
ER -