GLUTATHIONE LEVELS ARE REDUCED IN DIABETIC RAT RETINA BUT ARE NOT INFLUENCED BY ISCHEMIA FOLLOWED BY RECIRCULATION

Free radicals have recently been proposed to play a role in the develo pment of diabetic retinopathy. The aim of the present study was to exa mine whether the abnormal metabolism caused by diabetes and by ischemi a followed by recirculation interferes with a free radical enzyme defe nse system in the retina, ie, glutathione, Diabetes mellitus was induc ed by injecting streptozotocin ([STZ] 60 mg/kg body weight [BW] intrap eritoneally). After 2 and 6 months, respectively, glutathione levels w ere measured in the retina and compared against those of age-matched n ormal control rats. Retinal ischemia was induced by careful ligation o f the vessels and the accompanying optic nerve behind the left eye bul b. The right eye served as a control. After 90 minutes of ischemia, re tinal circulation was reestablished by removing the ligature. Two-mont h-old diabetic rats were kept for an additional 3 days and normal rats for 5 minutes, 15 minutes, or 3 days before they were killed for meas urement of glutathione. Retinal levels of glutathione were significant ly lower in g-month diabetic compared with 2-month diabetic rats (16.6 +/- 2.9 v 19.0 +/- 2.2 nmol/mg protein, P < .05) and B-month normal c ontrol rats (16.6 +/- 2.9 v 21.0 +/- 2.1 nmol/mg protein, P < .001). I schemia followed by recirculation did not influence the total tissue l evel of glutathione either in 2-month-old diabetic rats or in normal r ats. The present study indicates that the abnormal metabolism caused b y diabetes, rather than by changes in retinal circulation, results in an impaired defense mechanism against free radicals, a factor that may be of importance for the development of diabetic retinopathy. However , since glutathione levels in the present study were measured in the w hole retina, it cannot be excluded that particular cell types, such as vascular cells, show an alteration in glutathione that is masked by t he glutathione levels in the other nonvascular cells of the retina. St udies using other techniques are needed to further explore this subjec t. Copyright (C) 1998 by W.B. Saunders Company.