Co-Expression of Catalase and Superoxide Dismutase 2 in Mitochondria Reduces Cone Cell Death in Retinitis Pigmentosa (RP)

Abstract

Purpose: : To test over-expression of components of the endogenous antioxidant defense system in Oxidative damage contributes to cone cell death in RP.

Methods: : The effect on oxidative damage (ELISA for carbonyl adducts on proteins), cone density, and photopic ERGs was compared in rd1 mice vs. rd1 mice with ubiquitous over-expression of SOD1 (Sod1-rd1 mice), and rd10 mice vs. rd10 mice with inducible expression in the mitochondria of photoreceptors of SOD2 (Sod2-rd10), Catalase (Catalase-rd10), or both (Sod2/Catalase-rd10).

Results: : Compared to rd1 mice, Sod1-rd1 mice showed increased retinal carbonyl adducts and decreased photopic b-wave amplitudes at P25, and decreased cone density at P35. Compared to rd10 mice, carbonyl adducts were significantly greater in Sod2-rd10 mice at P35 and significantly less in Sod2/Catalase-rd10 mice at P50.At P50, Sod2/Catalase-rd10 mice had significantly higher photopic b-wave amplitudes and greater cone density than rd10, Sod2-rd10 or Catalase-rd10. There were no differences in scotopic b-wave amplitudes or ONL thickness among the four groups.

Conclusions: : Over-expression of SOD1 or 2 alone increase oxidative damage in rd1 or rd10 mice, whereas co-expression of SOD2 and Catalase in mitochondria of photoreceptors significantly reduced oxidative damage and preserved cone cell viability and function after rod cell death.

Keywords: retinal degenerations: hereditary • oxidation/oxidative or free radical damage • mitochondria