Abnormalities of retinal metabolism in diabetes or galactosemia. II. Comparison of gamma-glutamyl transpeptidase in retina and cerebral cortex, and effects of antioxidant therapy.
Levels of the intracellular antioxidant, glutathione, become subnormal in retina in diabetes or experimental galactosemia. In order to investigate the cause and significance of this abnormality, activity of gamma-glutamyl transpeptidase (an enzyme important in the synthesis and degradation of glutathione) and levels of reduced glutathione have been measured in retinas of diabetic rats and dogs and of experimentally galactosemic rats and dogs. Retinal gamma-glutamyl transpeptidase activity and glutathione level were significantly less than normal after 2 months of diabetes or galactosemia. In contrast, cerebral cortex from the same diabetic rats and galactosemic rats showed no significant reduction in either gamma-glutamyl transpeptidase activity or glutathione level. These different responses of the two tissues to hyperglycemia might help account for the difference in microvascular disease in these two tissues in diabetes. Consumption of the antioxidants, ascorbic acid (1.0%) plus alpha-tocopherol (0.1%), by diabetic rats and galactosemic rats inhibited the decrease of gamma-glutamyl transpeptidase activity and glutathione levels in retina, suggesting that defects in glutathione regulation in the retina are secondary to hyperglycemia-induced 'oxidative stress'.
Kowluru
R
R
Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison 53706-1532.
Kern
T S
TS
Engerman
R L
RL
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000201:enzymology*; D003930:Diabetic Retinopathy / Q000139:chemically induced / Q000188:drug therapy / Q000201:enzymology*; D004285:Dogs; D004359:Drug Therapy, Combination; D005693:Galactosemias / Q000139:chemically induced / Q000188:drug therapy / Q000201:enzymology*; D005978:Glutathione / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects / Q000201:enzymology*; D014810:Vitamin E / Q000008:administration & dosage / Q000494:pharmacology; D005723:gamma-Glutamyltransferase / Q000378:metabolism*
D000975:Antioxidants; D014810:Vitamin E; D005723:gamma-Glutamyltransferase; D005978:Glutathione; D001205:Ascorbic Acid