ENDOGENOUS ASCORBATE REGENERATES VITAMIN-E IN THE RETINA DIRECTLY ANDIN COMBINATION WITH EXOGENOUS DIHYDROLIPOIC ACID

Vitamin E (alpha-tocopherol) is the major lipid-soluble antioxidant of retinal membranes whose deficiency causes retinal degeneration. Its a ntioxidant function is realized via scavenging peroxyl radicals as a r esult of which phenoxyl radicals of alpha-tocopherol are formed. Our h ypothesis is that alpha-tocopherol phenoxyl radicals can be reduced by endogenous reductants in the retina, providing for alpha-tocopherol r ecycling. The results of this study demonstrate for the first time tha t: (i) endogenous ascorbate (vitamin C) in retinal homogenates and in rod outer segments is able to protect endogenous alpha-tocopherol agai nst oxidation induced by UV-irradiation by reducing the phenoxyl radic al of alpha-tocopherol, (ii) in the absence of ascorbate, neither endo genous nor exogenously added glutathione (GSH) is efficient in protect ing alpha-tocopherol against oxidation; (iii) GSH does not substantial ly enhance the protective effect of ascorbate against alpha-tocopherol oxidation; (iv) exogenous dihydrolipoic acid (DHLA), although ineffic ient 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 ret ina. The recycling of alpha-tocopherol opens new avenues for pharmacol ogical approaches to enhance antioxidants of the retina.