RGD Reference Report - Increased expression of catalase and superoxide dismutase 2 reduces cone cell death in retinitis pigmentosa. - Rat Genome Database

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Increased expression of catalase and superoxide dismutase 2 reduces cone cell death in retinitis pigmentosa.

Authors: Usui, S  Komeima, K  Lee, SY  Jo, YJ  Ueno, S  Rogers, BS  Wu, Z  Shen, J  Lu, L  Oveson, BC  Rabinovitch, PS  Campochiaro, PA 
Citation: Usui S, etal., Mol Ther. 2009 May;17(5):778-86. doi: 10.1038/mt.2009.47. Epub 2009 Mar 17.
RGD ID: 8158049
Pubmed: PMID:19293779   (View Abstract at PubMed)
PMCID: PMC2803613   (View Article at PubMed Central)
DOI: DOI:10.1038/mt.2009.47   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
retinitis pigmentosa  IDA 8158049; 8158049 RGD 
retinitis pigmentosa  ISOCAT (Homo sapiens)8158049; 8158049 RGD 
retinitis pigmentosa severityIMP 8158049human gene in a mouse modelRGD 
retinitis pigmentosa  ISOSod2 (Mus musculus)8158049; 8158049 RGD 
retinitis pigmentosa severityISOSOD1 (Homo sapiens)8158049; 8158049human gene in a mouse modelRGD 

Objects Annotated

Genes (Rattus norvegicus)
Cat  (catalase)
Sod1  (superoxide dismutase 1)
Sod2  (superoxide dismutase 2)

Genes (Mus musculus)
Cat  (catalase)
Sod1  (superoxide dismutase 1, soluble)
Sod2  (superoxide dismutase 2, mitochondrial)

Genes (Homo sapiens)
CAT  (catalase)
SOD1  (superoxide dismutase 1)
SOD2  (superoxide dismutase 2)


Additional Information