title: Clinicopathological features in anterior visual pathway in neuromyelitis optica.
abstract: OBJECTIVE
  Neuromyelitis optica spectrum disorder (NMOsd) is an autoimmune disorder of the central nervous system characterized by aquaporin-4 (AQP4) autoantibodies. The aim of this study was to elucidate the characteristics of involvement of the anterior visual pathway (AVP) and neurodegeneration via glia-neuron interaction in NMOsd.
  
  
  METHODS
  Thirty Japanese patients with serologically verified NMOsd were assessed with a neuro-ophthalmological study. Using 27 tissue blocks from 13 other cases of NMOsd, we performed neuropathological analysis of glial and neuroaxonal involvement in the AVP.
  
  
  RESULTS
  The AVP involvement in NMOsd was characterized by the following, compared to multiple sclerosis: (1) longitudinally extensive optic neuritis (ON); (2) more severe visual impairment and worse prognosis for ON; (3) unique AQP4 dynamics, including loss of AQP4 immunoreactivity on astrocytes with complement activation in ON lesions, loss of AQP4 immunoreactivity on Müller cells with no deposition of complement in the retinas, and densely packed AQP4 immunoreactivity on astrocytes in gliosis of secondary anterograde/retrograde degeneration in the optic nerves and retinal nerve fiber layer (RNFL); and (4) more severe neurodegeneration, including axonal accumulation of degenerative mitochondria and transient receptor potential melastatin 4 channel with complement-dependent astrocyte pathology in ON lesions, mild loss of horizontal cells, and RNFL thinning and loss of ganglion cells with abundance of AQP4(+) astrocytes, indicating secondary retrograde degeneration after ON.
  
  
  CONCLUSIONS
  Severe and widespread neuroaxonal damage and unique dynamics of astrocytes/Müller cells with alterations of AQP4 were prominent in the AVP and may be associated with poor visual function and prognosis in NMOsd.
authors.affiliation: Department of Neurology, Brain Research Institute, Niigata University, Niigata.
authors.forename: Mariko
authors.initials: M
authors.lastname: Hokari
authors.affiliation: Department of Neurology, Brain Research Institute, Niigata University, Niigata.
authors.forename: Akiko
authors.initials: A
authors.lastname: Yokoseki
authors.affiliation: Department of Neurology, Brain Research Institute, Niigata University, Niigata.
authors.forename: Musashi
authors.initials: M
authors.lastname: Arakawa
authors.affiliation: Department of Neurology, Brain Research Institute, Niigata University, Niigata.
authors.forename: Etsuji
authors.initials: E
authors.lastname: Saji
authors.affiliation: Department of Neurology, Brain Research Institute, Niigata University, Niigata.
authors.forename: Kaori
authors.initials: K
authors.lastname: Yanagawa
authors.affiliation: Department of Neurology, Brain Research Institute, Niigata University, Niigata.
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Yanagimura
authors.affiliation: Department of Pathology, Brain Research Institute, Niigata University, Niigata.
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Toyoshima
authors.affiliation: Department of Neurosurgery, Brain Research Institute, Niigata University, Niigata.
authors.forename: Kouichirou
authors.initials: K
authors.lastname: Okamoto
authors.affiliation: Center for Integrated Human Brain Science, Brain Research Institute, Niigata University, Niigata.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ueki
authors.affiliation: Department of Ophthalmology, Niigata University, Niigata.
authors.forename: Tetsuhisa
authors.initials: T
authors.lastname: Hatase
authors.affiliation: Department of Pathology, Niigata University Medical and Dental Hospital, Niigata.
authors.forename: Riuko
authors.initials: R
authors.lastname: Ohashi
authors.affiliation: Department of Ophthalmology, Niigata University, Niigata.
authors.forename: Takeo
authors.initials: T
authors.lastname: Fukuchi
authors.affiliation: Department of Medical Informatics, Niigata University Medical and Dental Hospital, Niigata.
authors.forename: Kohei
authors.initials: K
authors.lastname: Akazawa
authors.affiliation: Department of Brain Disease Research, Shinshu University School of Medicine, Matsumoto, Nagano, Japan.
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Yamada
authors.affiliation: Department of Pathology, Brain Research Institute, Niigata University, Niigata.
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Kakita
authors.affiliation: Department of Pathology, Brain Research Institute, Niigata University, Niigata.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Department of Neurology, Brain Research Institute, Niigata University, Niigata.
authors.forename: Masatoyo
authors.initials: M
authors.lastname: Nishizawa
authors.affiliation: Department of Neurology, Brain Research Institute, Niigata University, Niigata.
authors.forename: Izumi
authors.initials: I
authors.lastname: Kawachi
mesh_terms: D000328:Adult; D051401:Aquaporin 4 / Q000276:immunology*; D001253:Astrocytes / Q000276:immunology / Q000473:pathology; D001369:Axons / Q000276:immunology / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D009103:Multiple Sclerosis / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D009471:Neuromyelitis Optica / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D009902:Optic Neuritis / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D014786:Vision Disorders / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D014795:Visual Pathways / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology
chemical_list: D051401:Aquaporin 4