Endogenous ascorbate regenerates vitamin E in the retina directly and in combination with exogenous dihydrolipoic acid

Curr Eye Res. 1995 Mar;14(3):181-9. doi: 10.3109/02713689509033513.


Vitamin E (alpha-tocopherol) is the major lipid-soluble antioxidant of retinal membranes whose deficiency causes retinal degeneration. Its antioxidant function is realized via scavenging peroxyl radicals as a result of which phenoxyl radicals of alpha-tocopherol are formed. Our hypothesis is that alpha-tocopherol phenoxyl radicals can be reduced by endogenous reductants in the retina, providing for alpha-tocopherol recycling. The results of this study demonstrate for the first time that: (i) endogenous ascorbate (vitamin C) in retinal homogenates and in rod outer segments is able to protect endogenous alpha-tocopherol against oxidation induced by UV-irradiation by reducing the phenoxyl radical of alpha-tocopherol, (ii) in the absence of ascorbate, neither endogenous nor exogenously added glutathione (GSH) is efficient in protecting alpha-tocopherol against oxidation; (iii) GSH does not substantially enhance the protective effect of ascorbate against alpha-tocopherol oxidation; (iv) exogenous dihydrolipoic acid (DHLA), although inefficient in direct reduction of the alpha-tocopherol phenoxyl radical, is able to enhance the protective effect of ascorbate by regenerating it from dehydroascorbate. Thus, regeneration of alpha-tocopherol from its phenoxyl radical can enhance its antioxidant effectiveness in the retina. The recycling of alpha-tocopherol opens new avenues for pharmacological approaches to enhance antioxidants of the retina.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Ascorbic Acid / physiology*
  • Chromatography, High Pressure Liquid
  • Dehydroascorbic Acid / metabolism
  • Electron Spin Resonance Spectroscopy
  • Free Radicals
  • Glutathione / pharmacology
  • Male
  • Oxidation-Reduction
  • Rats
  • Rats, Sprague-Dawley
  • Retina / drug effects
  • Retina / metabolism*
  • Retina / radiation effects
  • Thioctic Acid / analogs & derivatives*
  • Thioctic Acid / pharmacology
  • Ultraviolet Rays
  • Vitamin E / biosynthesis*


  • Free Radicals
  • Vitamin E
  • Thioctic Acid
  • dihydrolipoic acid
  • Glutathione
  • Ascorbic Acid
  • Dehydroascorbic Acid