title: Lipid peroxidation and peroxynitrite in retinal ischemia-reperfusion injury.
abstract: OBJECTIVE
  To investigate whether lipid peroxides play a role in retinal cell death due to ischemia-reperfusion injury, whether recombinant human thioredoxin (rhTRX) treatment reduces production of lipid peroxides of the retina, and whether such treatment reduces the number of cells expressing c-Jun and cyclin D1.
  
  
  METHODS
  Retinal ischemia was induced in rats by increasing the intraocular pressure to 110 mm Hg for 60 minutes. After reperfusion, immunohistochemical staining for lipid peroxide, peroxynitrite, c-Jun, and cyclin D1 and propidium iodide (PI) staining were performed on retinal sections from animals treated intravenously with and without rhTRX, a free radical scavenger. Quantitative analyses of PI-, c-Jun-, and cyclin D1-positive cells were performed after the ischemic insult. Concentration of lipid peroxides in the retina was determined by the thiobarbituric acid assay.
  
  
  RESULTS
  Specific immunostaining for lipid peroxides was seen in the ganglion cell layer at 6 hours after reperfusion, in the inner nuclear layer at 12 hours, and in the outer nuclear layer at 48 hours. Time course studies for PI-positive cells in the three nuclear layers coincided with those of specific immunostaining for lipid peroxides. The specific immunostaining was weakened by pre- and posttreatment with 0.5 mg of rhTRX. The number of PI-, c-Jun-, and cyclin D1-positive cells and the concentration of lipid peroxides were significantly decreased by treatment with rhTRX compared with those of vehicle-treated control rats (P: < 0. 01).
  
  
  CONCLUSIONS
  Lipid peroxides formed by free radicals may play a role in neuronal cell death in retinal ischemia-reperfusion injury.
authors.affiliation: Department of Ophthalmology, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Shibuki
authors.forename: N
authors.initials: N
authors.lastname: Katai
authors.forename: J
authors.initials: J
authors.lastname: Yodoi
authors.forename: K
authors.initials: K
authors.lastname: Uchida
authors.forename: N
authors.initials: N
authors.lastname: Yoshimura
mesh_terms: D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D016923:Cell Death; D019938:Cyclin D1 / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D016166:Free Radical Scavengers / Q000627:therapeutic use; D015227:Lipid Peroxidation; D008054:Lipid Peroxides / Q000378:metabolism*; D008297:Male; D009566:Nitrates / Q000378:metabolism*; D011419:Propidium / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000627:therapeutic use; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D012160:Retina / Q000378:metabolism* / Q000473:pathology; D012164:Retinal Diseases / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D017392:Thiobarbituric Acid Reactive Substances; D013879:Thioredoxins / Q000627:therapeutic use
chemical_list: D000447:Aldehydes; D016166:Free Radical Scavengers; D008054:Lipid Peroxides; D009566:Nitrates; D016755:Proto-Oncogene Proteins c-jun; D011994:Recombinant Proteins; D017392:Thiobarbituric Acid Reactive Substances; D019938:Cyclin D1; C039642:peroxynitric acid; D011419:Propidium; D013879:Thioredoxins; C027576:4-hydroxy-2-nonenal