Overexpression of SOD in retina: Need for increase in H 2O 2-detoxifying enzyme in same cellular compartment

Shinichi Usui, Brian C. Oveson, Takeshi Iwase, Lili Lu, Sun Young Lee, Young Joon Jo, Zhihao Wu, Eun Young Choi, Richard J. Samulski, Peter A. Campochiaro

Research output: Contribution to journalArticlepeer-review

Abstract

In retinitis pigmentosa (RP), various mutations cause rod photoreceptor cell death leading to increased oxygen levels in the outer retina, progressive oxidative damage to cones, and gradual loss of cone cell function. We have been exploring the potential of overexpressing components of the endogenous antioxidant defense system to preserve cone cell function in rd10 +/+ mice, a model of RP. rd10 +/+ mice deficient in superoxide dismutase 1 (SOD1) showed increased levels of superoxide radicals and carbonyl adducts (a marker of oxidative damage) in the retina and more rapid loss of cone function than rd10 +/+ mice with normal levels of SOD1. This suggests that SOD1 is an important component of the antioxidant defense system of cones, but increased expression of SOD1 in rd10 +/+ mice increased oxidative damage and accelerated the loss of cone function. Coexpression of SOD1 with glutathione peroxidase 4 (Gpx4), which like SOD1 is localized in the cytoplasm, but not with catalase targeted to the mitochondria, reduced oxidative damage in the retina and significantly slowed the loss of cone cell function in rd10 +/+ mice. Gene transfer resulting in increased expression of SOD2, but not coexpression of SOD2 and mitochondrial Gpx4, resulted in high levels of H 2O 2 in the retina. These data suggest that to provide benefit in RP, overexpression of an SOD must be combined with expression of a peroxide-detoxifying enzyme in the same cellular compartment.

Original languageEnglish (US)
Pages (from-to)1347-1354
Number of pages8
JournalFree Radical Biology and Medicine
Volume51
Issue number7
DOIs
StatePublished - Oct 1 2011

Keywords

  • Catalase
  • Free radicals
  • Glutathione peroxidase
  • Photoreceptors
  • Reactive oxygen species
  • Retina
  • Retinitis pigmentosa

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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