Lipid peroxidation and peroxynitrite in retinal ischemia-reperfusion injury

Invest Ophthalmol Vis Sci. 2000 Oct;41(11):3607-14.


Purpose: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehydes / metabolism
  • Animals
  • Cell Death
  • Cyclin D1 / metabolism
  • Fluorescent Antibody Technique, Indirect
  • Free Radical Scavengers / therapeutic use
  • Lipid Peroxidation*
  • Lipid Peroxides / metabolism*
  • Male
  • Nitrates / metabolism*
  • Propidium / metabolism
  • Proto-Oncogene Proteins c-jun / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins / therapeutic use
  • Reperfusion Injury / drug therapy
  • Reperfusion Injury / metabolism*
  • Reperfusion Injury / pathology
  • Retina / metabolism*
  • Retina / pathology
  • Retinal Diseases / drug therapy
  • Retinal Diseases / metabolism*
  • Retinal Diseases / pathology
  • Thiobarbituric Acid Reactive Substances
  • Thioredoxins / therapeutic use


  • Aldehydes
  • Free Radical Scavengers
  • Lipid Peroxides
  • Nitrates
  • Proto-Oncogene Proteins c-jun
  • Recombinant Proteins
  • Thiobarbituric Acid Reactive Substances
  • Cyclin D1
  • peroxynitric acid
  • Propidium
  • Thioredoxins
  • 4-hydroxy-2-nonenal