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Yoshimichi Matsunaga, Kezuka Takeshi, Kouji Fujita, Nagahisa Matsuyama, Ryusaku Matsuda, Naoyuki Yamakawa, Masao Yoshikawa, Masahiko Kuroda, Hiroshi Goto; Correlation between Visual Evoked Potential and Histopathology in Experimental Autoimmune Optic Neuritis. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2983.
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© ARVO (1962-2015); The Authors (2016-present)
To elucidate the correlation between visual evoked potential (VEP) and histopathology at different time points after induction of experimental autoimmune optic neuritis (EAON).
EAON was induced in C57BL/6 mice by subcutaneous immunization with an emulsified mixture of MOG35-55 peptide, dimethyl sulfoxide, and complete Freund’s adjuvant. Bordetella pertusis toxin was also injected intraperitoneally on the day of immunization. VEP was measured on days 7, 14, 21, 28, and 42 post-immunization. After VEP measurement, the mice were killed, and their eyes were enucleated for histopathological studies. Immunohistochemical staining was performed using cell-specific markers for characterization of infiltrating cells: CD3 (T cells), Olig2 (oligodendrocytes), GFAP (astrocytes), MBP (myelin protein), and Iba-1 (microglia). Moreover, axon counting was performed using toluidine blue staining. All experiments were approved by the Institutional Animal Research Committee of Tokyo Medical University and conformed to the Association for Research in Vision and Ophthalmology Statement for the Use of Animals in Ophthalmic and Vision Research.
VEP latency prolongation was significantly observed on day 21. Axon degeneration was observed as early as on day 14. Activated microglia infiltration was also observed on day 14, i.e., before T-cell infiltration, which peaked on day 21. Astrocytes were significantly activated on day 14, and their levels showed an increase during the course. Demyelination, confirmed by MBP staining, was observed on day 21. Oligodendrocyte cell density decreased on day 21.
Microglial infiltration into the optic nerve in EAON preceded VEP latency prolongation. Demyelination of the optic nerve coincided with latency prolongation. These findings may contribute to the understanding of the pathophysiology of optic neuritis and to the development of more effective therapeutic strategy for refractory optic neuritis.
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