title: Change of redox status and modulation by thiol replenishment in retinal photooxidative damage.
abstract: OBJECTIVE
  Cellular or tissue reduction-oxidation (redox) is crucial in various diseases. The present study was conducted to analyze how tissue redox status is affected by photooxidative stress and whether the exogenous thiol antioxidant N-acetylcysteine (NAC) affects photooxidative stress-induced retinal damage.
  
  
  METHODS
  Mice were intraperitoneally injected with either NAC (250 mg/kg) or phosphate-buffered saline (PBS) and exposed to white fluorescent light (8000 lux) for 2 hours. Levels of thioredoxin (TRX), glutaredoxin (GRX), and glutathione (GSH), endogenous regulators of redox; 4-hydroxy-2-nonenal (HNE)-modified protein, a marker of lipid peroxidation; and nuclear factor (NF)-kappaB, a redox-sensitive transcription factor in retinal samples, was measured by immunohistochemistry and Western blot or enzymatic recycling assay. Light-induced retinal damage estimated by electroretinography and quantitative immunohistochemistry for 8-hydroxy-2-deoxyguanosine (8OHdG index), a marker of oxidative stress-induced DNA damage, was compared in NAC- and PBS-treated mice.
  
  
  RESULTS
  Upregulation of TRX and HNE-modified protein, decrease of GSH, and nuclear translocation of NF-kappaB were noted after light exposure in PBS-treated mice. These changes were suppressed in NAC-treated mice compared with PBS-treated mice. GRX was not upregulated after light exposure in any mice. The a- and b-wave amplitudes were significantly higher, and the 8OHdG index was significantly lower after light exposure in NAC-treated mice than in PBS-treated mice.
  
  
  CONCLUSIONS
  Retinal redox status is altered by intense light and is normalized partially by the effect of NAC on TRX and GSH tissue levels. Manipulation of the tissue redox state by exogenous thiol replenishment may be a useful strategy to prevent retinal photooxidative damage.
authors.affiliation: Department of Ophthalmology, Shimane Medical University, 89-1 Enya, Izumo, Shimane 693-8501, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Tanito
authors.forename: Akira
authors.initials: A
authors.lastname: Nishiyama
authors.forename: Toru
authors.initials: T
authors.lastname: Tanaka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Masutani
authors.forename: Hajime
authors.initials: H
authors.lastname: Nakamura
authors.forename: Junji
authors.initials: J
authors.lastname: Yodoi
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ohira
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D003432:Cross-Linking Reagents / Q000494:pharmacology; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D004596:Electroretinography; D054477:Glutaredoxins; D005978:Glutathione / Q000378:metabolism; D008027:Light; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000528:radiation effects*; D010088:Oxidoreductases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D011833:Radiation Injuries, Experimental / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D012160:Retina / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D012162:Retinal Degeneration / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013879:Thioredoxins / Q000378:metabolism
chemical_list: D003432:Cross-Linking Reagents; D054477:Glutaredoxins; D016328:NF-kappa B; D011506:Proteins; D013879:Thioredoxins; D000080242:8-Hydroxy-2'-Deoxyguanosine; D010088:Oxidoreductases; D003849:Deoxyguanosine; D005978:Glutathione; D000111:Acetylcysteine