title: Retinal light damage: structural and functional effects of the antioxidant glutathione peroxidase-1.
abstract: OBJECTIVE
  The role of the antioxidant enzyme glutathione peroxidase-1 (GPx1) in protecting the retina against photo-oxidative damage was investigated in GPx1-deficient and wild-type mice.
  
  
  METHODS
  Albino GPx1-deficient and age-matched wild-type mice were examined. Baseline electroretinograms (ERGs) were recorded. Thereafter, mice were exposed to intense light for 12 hours. After a 24-hour recovery in darkness, post-light-insult ERGs were recorded and compared with baseline. Structural effects of light insult were evaluated by retinal histology. Antioxidant expression was investigated by quantitative reverse transcription-PCR (qRT-PCR).
  
  
  RESULTS
  Light insult significantly affected ERG responses, with reduced a- and b-wave amplitudes. Structurally, photoreceptor layers were predominantly affected. As expected, GPx1 expression was negligible in GPx1-deficient mice but was upregulated in wild-type mice in response to light insult. Similarly, hemeoxygenase-1 and thioredoxin-1 expression increased significantly in wild-type retinas after light exposure. Catalase, GPx isoforms (GPx2 to -4), peroxiredoxin-6, glutaredoxin-1, and thioredoxin-2 expression was unaffected by GPx1 deficiency and light insult, whereas significant increases in glutaredoxin-2 occurred in non-light-exposed (baseline) GPx1-deficient retinas. Compared with baseline wild-type retinas, lipid peroxidation (TBARS assay), an indicator of oxidative stress, was elevated in baseline GPx1-deficient retinas. Unexpectedly, the light insult induced diminution of retinal function, in terms of ERG amplitude, and structural damage was significantly greater in wild-type than in with GPx1-deficient retinas.
  
  
  CONCLUSIONS
  The data showing increased oxidative damage in baseline GPx-deficient retina give rise to the hypothesis that increased oxidative stress provides a "preconditioning" environment in which protective mechanisms paradoxically render GPx1-deficient retinas less vulnerable to light-induced oxidative damage. This study identified glutaredoxin-2 as a potential candidate.
authors.affiliation: Ophthalmology Research Group, Monash University, Department of Surgery, Monash Medical Centre, Clayton, Victoria, Australia.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Gosbell
authors.forename: Nada
authors.initials: N
authors.lastname: Stefanovic
authors.forename: Lyndee L
authors.initials: LL
authors.lastname: Scurr
authors.forename: Josefa
authors.initials: J
authors.lastname: Pete
authors.forename: Ismail
authors.initials: I
authors.lastname: Kola
authors.forename: Ian
authors.initials: I
authors.lastname: Favilla
authors.forename: Judy B
authors.initials: JB
authors.lastname: de Haan
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000502:physiology*; D002374:Catalase / Q000378:metabolism; D004596:Electroretinography / Q000528:radiation effects; D005786:Gene Expression Regulation; D054477:Glutaredoxins; D005979:Glutathione Peroxidase / Q000172:deficiency / Q000502:physiology*; D008027:Light; D015227:Lipid Peroxidation; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D018384:Oxidative Stress; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism; D010544:Peroxidases / Q000235:genetics / Q000378:metabolism; D054465:Peroxiredoxin VI; D054464:Peroxiredoxins; D012333:RNA, Messenger / Q000378:metabolism; D011833:Radiation Injuries, Experimental / Q000201:enzymology* / Q000503:physiopathology; D012160:Retina / Q000503:physiopathology / Q000528:radiation effects*; D012164:Retinal Diseases / Q000201:enzymology* / Q000503:physiopathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017392:Thiobarbituric Acid Reactive Substances; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D000094765:Glutathione Peroxidase GPX1
chemical_list: D000975:Antioxidants; C516006:Glrx protein, mouse; C516009:Glrx2 protein, mouse; D054477:Glutaredoxins; D008565:Membrane Proteins; D012333:RNA, Messenger; D017392:Thiobarbituric Acid Reactive Substances; C516112:Txn2 protein, mouse; D013879:Thioredoxins; D010088:Oxidoreductases; D010544:Peroxidases; D054465:Peroxiredoxin VI; D054464:Peroxiredoxins; C515983:Prdx6 protein, mouse; D002374:Catalase; D005979:Glutathione Peroxidase; D000094765:Glutathione Peroxidase GPX1; C000722068:Gpx1 protein, mouse