Retinal ganglion cell loss in superoxide dismutase 1 deficiency

Kenya Yuki, Yoko Ozawa, Tetsu Yoshida, Toshihide Kurihara, Manabu Hirasawa, Naoki Ozeki, Daisuke Shiba, Kousuke Noda, Susumu Ishida, Kazuo Tsubota

Research output: Contribution to journalArticlepeer-review

46 Citations (Scopus)

Abstract

Purpose. 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.

Original languageEnglish
Pages (from-to)4143-4150
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume52
Issue number7
DOIs
Publication statusPublished - 2011 Jun

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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