AN ALDOSE REDUCTASE INHIBITOR, TAT, PREVENTS ELECTRORETINOGRAPHIC ABNORMALITIES AND ADP-INDUCED HYPERAGGREGABILITY IN STREPTOZOTOCIN-INDUCED DIABETIC RATS

Rats with streptozotocin-induced diabetes were oral given TAT, a poten t aldose reductase inhibitor a dose of 10 mg kg(-1) day(-1) or 40 mg k g(-1) for 30 days. Prolongation of the peak latency of oscillatory pot entials in the b-wave of the electroretinogram (ERG), which is associa ted with retinal Muller cell dysfunction, was significantly improved b y treatment with TAT as compared with untreated diabetic rats [Sigma(O -1 + O-2 + O-3) was 106.8 +/- 1.8 ms in normal controls (NC), 118.2 +/ - 1.1 ms in diabetic controls (DC) (P < 0.001 vs. NC), 110.8 +/- 1.5 m s with 10 mg kg(-1) TAT (P < 0.001 vs. DC) and 111.4 +/- 1.6 ms with 4 0 mg kg(-1) TAT (P < 0.01 vs. DC)]. The improvement in ERG abnormaliti es in diabetic rats was accompanied by partial reduction of elevated s orbitol levels in the retina and erythrocytes, and by correction of pl atelet hyperaggregability. The authors' findings suggest that a better understanding of the mechanism by which TAT acts may provide new insi ghts into the pathogenesis of hyperglycaemic retinal dysfunction and c ontribute to establishing effective therapy for diabetic retinopathy.