Increased expression of catalase and superoxide dismutase 2 reduces cone cell death in retinitis pigmentosa.
Oxidative and nitrosative damage are major contributors to cone cell death in retinitis pigmentosa (RP). In this study, we explored the effects of augmenting components of the endogenous antioxidant defense system in models of RP, rd1, and rd10 mice. Unexpectedly, overexpression of superoxide dismutase 1 (SOD1) in rd1 mice increased oxidative damage and accelerated cone cell death. With an elaborate mating scheme, genetically engineered rd10 mice with either inducible expression of SOD2, Catalase, or both in photoreceptor mitochondria were generated. Littermates with the same genetic background that did not have increased expression of SOD2 nor Catalase provided ideal controls. Coexpression of SOD2 and Catalase, but not either alone, significantly reduced oxidative damage in the retinas of postnatal day (P) 50 rd10 mice as measured by protein carbonyl content. Cone density was significantly greater in P50 rd10 mice with coexpression of SOD2 and Catalase together than rd10 mice that expressed SOD2 or Catalase alone, or expressed neither. Coexpression of SOD2 and Catalase in rd10 mice did not slow rod cell death. These data support the concept of bolstering the endogenous antioxidant defense system as a gene-based treatment strategy for RP, and also indicate that coexpression of multiple components may be needed.
Usui
Shinichi
S
Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-9277, USA.
Komeima
Keiichi
K
Lee
Sun Young
SY
Jo
Young-Joon
YJ
Ueno
Shinji
S
Rogers
Brian S
BS
Wu
Zhihao
Z
Shen
Jikui
J
Lu
Lili
L
Oveson
Brian C
BC
Rabinovitch
Peter S
PS
Campochiaro
Peter A
PA
D000818:Animals; D002374:Catalase / Q000235:genetics / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005838:Genotype; D015151:Immunoblotting; D051379:Mice; D008822:Mice, Transgenic; D050050:Protein Carbonylation / Q000235:genetics; D012160:Retina / Q000378:metabolism / Q000473:pathology; D017949:Retinal Cone Photoreceptor Cells / Q000166:cytology* / Q000378:metabolism*; D012174:Retinitis Pigmentosa / Q000235:genetics / Q000473:pathology*; D013482:Superoxide Dismutase / Q000235:genetics / Q000502:physiology*; D013481:Superoxides / Q000378:metabolism; D000099156:Superoxide Dismutase 2
D002374:Catalase; D013482:Superoxide Dismutase; D013481:Superoxides; D000099156:Superoxide Dismutase 2