Retinal dysfunction and progressive retinal cell death in SOD1-deficient mice

Kouhei Hashizume, Manabu Hirasawa, Yutaka Imamura, Setsuko Noda, Takahiko Shimizu, Kei Shinoda, Toshihide Kurihara, Kousuke Noda, Yoko Ozawa, Susumu Ishida, Yozo Miyake, Takuji Shirasawa, Kazuo Tsubota

Research output: Contribution to journalArticle

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Abstract

The superoxide dismutase (SOD) family is a major antioxidant system, and deficiency of Cu,Zn-superoxide dismutase (SOD1) in mice leads to many different phenotypes that resemble accelerated aging. The purpose of this study was to examine the morphology and physiology of the sensory retina in Sod1 -/- mice. The amplitudes of the a- and b-waves of electroretinograms elicited by stimuli of different intensity were reduced in senescent Sod1 -/- mice, and this reduction in amplitude was more pronounced with increasing age. Retinal morphometric analyses showed a reduced number of nuclei in both the inner nuclear cell layer and outer nuclear cell layer. Electron microscopy revealed swollen cells and degenerated mitochondria in the inner nuclear cell and outer nuclear cell layer of senescent Sod1-/- mice indicating necrotic cell death. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling revealed no significant differences in the number of apoptotic cells between Sod1-/- and wild-type mice, and activated caspase-3 could not be detected in the retina of Sod1-/- mice. In addition to the age-related macular degeneration-like phenotypes previously reported, Sod1-/- mice also present progressive retinal degeneration. Our results indicate that Sod1-/- mice may be a good model system in which to study the mechanism of reactive oxygen species-mediated retinal degeneration.

Original languageEnglish
Pages (from-to)1325-1331
Number of pages7
JournalAmerican Journal of Pathology
Volume172
Issue number5
DOIs
Publication statusPublished - 2008 May

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Cell Death
Retinal Degeneration
Retina
Phenotype
DNA Nucleotidylexotransferase
Macular Degeneration
Superoxide Dismutase
Reactive Oxygen Species
Electron Microscopy
Mitochondria
Cell Count
Antioxidants

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Retinal dysfunction and progressive retinal cell death in SOD1-deficient mice. / Hashizume, Kouhei; Hirasawa, Manabu; Imamura, Yutaka; Noda, Setsuko; Shimizu, Takahiko; Shinoda, Kei; Kurihara, Toshihide; Noda, Kousuke; Ozawa, Yoko; Ishida, Susumu; Miyake, Yozo; Shirasawa, Takuji; Tsubota, Kazuo.

In: American Journal of Pathology, Vol. 172, No. 5, 05.2008, p. 1325-1331.

Research output: Contribution to journalArticle

Hashizume, K, Hirasawa, M, Imamura, Y, Noda, S, Shimizu, T, Shinoda, K, Kurihara, T, Noda, K, Ozawa, Y, Ishida, S, Miyake, Y, Shirasawa, T & Tsubota, K 2008, 'Retinal dysfunction and progressive retinal cell death in SOD1-deficient mice', American Journal of Pathology, vol. 172, no. 5, pp. 1325-1331. https://doi.org/10.2353/ajpath.2008.070730
Hashizume K, Hirasawa M, Imamura Y, Noda S, Shimizu T, Shinoda K et al. Retinal dysfunction and progressive retinal cell death in SOD1-deficient mice. American Journal of Pathology. 2008 May;172(5):1325-1331. https://doi.org/10.2353/ajpath.2008.070730
Hashizume, Kouhei ; Hirasawa, Manabu ; Imamura, Yutaka ; Noda, Setsuko ; Shimizu, Takahiko ; Shinoda, Kei ; Kurihara, Toshihide ; Noda, Kousuke ; Ozawa, Yoko ; Ishida, Susumu ; Miyake, Yozo ; Shirasawa, Takuji ; Tsubota, Kazuo. / Retinal dysfunction and progressive retinal cell death in SOD1-deficient mice. In: American Journal of Pathology. 2008 ; Vol. 172, No. 5. pp. 1325-1331.
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