title: Retinal ganglion cell loss in superoxide dismutase 1 deficiency.
abstract: OBJECTIVE
  To investigate the influence of deficiency in superoxide dismutase (SOD) 1, a major antioxidative enzyme, on retinal ganglion cells (RGCs).
  
  
  METHODS
  In the SOD1 total knockout (SOD1-deficient) mice, the level of superoxide anion was measured using dihydroethidium. The number of RGCs was counted in both the retinal sections and the flat-mount retinas after retrograde labeling. Thickness of nerve fiber layer (NFL) was measured in the sections, and the amount of neurofilament protein was measured by immunoblot analysis. Pattern electroretinogram (ERG), which reflects the function of retinal ganglion cells, dark-adapted ERG, and cone ERG were performed. The intraocular pressure (IOP) was measured with an induction-impact tonometer. The levels of SOD-1 and -2 were measured by ELISA, in the serum of 47 newly diagnosed consecutive normal tension glaucoma (NTG) patients and 44 consecutive control subjects.
  
  
  RESULTS
  The level of superoxide anion in the RGC layer was significantly higher in 24-week-old SOD1-deficient mice than in wild-type mice. The RGC number was significantly reduced in 24-week-old SOD1-deficient mice, although they were not in 8-week-old mice. The NFL thickness and neurofilament protein were reduced in 24-week-old SOD1-deficient mice. The amplitude of pattern ERG was significantly reduced, although dark-adapted and cone ERGs showed no impairment, in 24-week-old SOD1-deficient mice. The IOP level was not changed in the SOD1-deficient mice. The serum level of SOD1, but not SOD2, was significantly lower in the NTG patients than in the healthy controls.
  
  
  CONCLUSIONS
  SOD1 deficiency causes RGC vulnerability, which may be involved in the underlying condition of NTG.
authors.affiliation: Laboratory of Retinal Cell Biology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Kenya
authors.initials: K
authors.lastname: Yuki
authors.forename: Yoko
authors.initials: Y
authors.lastname: Ozawa
authors.forename: Tetsu
authors.initials: T
authors.lastname: Yoshida
authors.forename: Toshihide
authors.initials: T
authors.lastname: Kurihara
authors.forename: Manabu
authors.initials: M
authors.lastname: Hirasawa
authors.forename: Naoki
authors.initials: N
authors.lastname: Ozeki
authors.forename: Daisuke
authors.initials: D
authors.lastname: Shiba
authors.forename: Kousuke
authors.initials: K
authors.lastname: Noda
authors.forename: Susumu
authors.initials: S
authors.lastname: Ishida
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tsubota
mesh_terms: D000368:Aged; D000375:Aging; D000818:Animals; D002452:Cell Count; D003623:Dark Adaptation; D004596:Electroretinography / Q000379:methods; D005260:Female; D006801:Humans; D007429:Intraocular Pressure; D057066:Low Tension Glaucoma / Q000097:blood* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D009412:Nerve Fibers / Q000378:metabolism / Q000473:pathology; D016900:Neurofilament Proteins / Q000378:metabolism; D017949:Retinal Cone Photoreceptor Cells; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000473:pathology*; D013482:Superoxide Dismutase / Q000097:blood* / Q000172:deficiency*; D000072105:Superoxide Dismutase-1; D013481:Superoxides / Q000378:metabolism
chemical_list: D016900:Neurofilament Proteins; C000606290:SOD1 protein, human; D013481:Superoxides; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1