title: Visual functional and histopathological correlation in experimental autoimmune optic neuritis.
abstract: OBJECTIVE
  To elucidate the correlation between visual threshold of optokinetic tracking (OKT), visual evoked potential (VEP), and histopathology at different time points after induction of experimental autoimmune optic neuritis (EAON).
  
  
  METHODS
  EAON was induced in C57BL/6 mice by subcutaneous immunization with an emulsified mixture of myelin oligodendrocyte glycoprotein (MOG)(35-55) peptide. OKT and VEP were measured on days 7, 14, 21, 28, and 42 postimmunization. After VEP measurements, the mice were killed and their eyes were enucleated for histopathological studies. Immunohistochemical staining was performed using cell-specific markers for characterization of cells in the optic nerve: CD3 (T cells), Iba-1 (microglia), MBP (myelin basic protein), and neurofilament (axons).
  
  
  RESULTS
  Functionally, OKT threshold decreased as early as day 7, and VEP latency was significantly prolonged on day 21. Axon degeneration was observed as early as day 14. Activated microglia infiltration was also observed on day 14, before T cell infiltration, which peaked on day 21. Demyelination, confirmed by MBP staining, was observed on day 21.
  
  
  CONCLUSIONS
  Microglial infiltration in the optic nerve coincided with decline in OKT threshold and preceded VEP latency prolongation, while VEP latency prolongation coincided with T cell infiltration and demyelination of the optic nerve. These findings may contribute to understanding of the pathophysiology of optic neuritis and future development of more effective therapeutic strategy for refractory optic neuritis.
authors.affiliation: Department of Ophthalmology, Tokyo Medical University, Shinjuku-ku, Tokyo, Japan.
authors.forename: Yoshimichi
authors.initials: Y
authors.lastname: Matsunaga
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kezuka
authors.forename: Xiaoming
authors.initials: X
authors.lastname: An
authors.forename: Kouji
authors.initials: K
authors.lastname: Fujita
authors.forename: Nagahisa
authors.initials: N
authors.lastname: Matsuyama
authors.forename: Ryusaku
authors.initials: R
authors.lastname: Matsuda
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Usui
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Yamakawa
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kuroda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Goto
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology; D017252:CD3 Complex / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D005074:Evoked Potentials, Visual / Q000502:physiology*; D007124:Immunoenzyme Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000378:metabolism; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D004676:Myelin Basic Protein / Q000378:metabolism; D063308:Myelin-Oligodendrocyte Glycoprotein; D009444:Neuritis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D017120:Nystagmus, Optokinetic / Q000502:physiology*; D009900:Optic Nerve / Q000503:physiopathology*; D009902:Optic Neuritis / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D010446:Peptide Fragments; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: C491049:Aif1 protein, mouse; D017252:CD3 Complex; D002135:Calcium-Binding Proteins; D008840:Microfilament Proteins; D004676:Myelin Basic Protein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55)