Influence of Glutathione on Retinal Function in the Diabetic Rat

Abstract

Purpose: : Electroretinogram (ERG) signals are altered by diabetes, reflective of neuronal signaling dysfunction. The present experiments were designed to investigate, in a rat model, the possible benefit of glutathione (GSH) supplementation on the diabetic ERG.

Methods: : Male RCC Wistar rats were injected with streptozotocin (60 mg/kg) to induce hyperglycemia (N=11), or injected with vehicle as a control (N=6). Six of the diabetic rats were given 600 mg/kg/day GSH in drinking water for the final 3 weeks of an 8-week period of hyperglycemia. At the end of the 8 weeks, an ERG procedure using 7 scotopic flash intensities was performed on the dark-adapted anesthetized rats, with the eyes removed just prior to euthanasia for retinal/vitreous GSH measurements. ERG parameters included the a-wave, b-wave, oscillatory potentials, and the corresponding implicit times.

Results: : Untreated diabetic rats were found to have prolonged b-wave implicit times in 3/7 of the scotopic intensities (p<0.05), indicative of retinal dysfunction, with this alteration attenuated by GSH treatment. No other ERG parameters were altered significantly by diabetes, although this possibly was due to variability in GSH. Retinal GSH was > 50 nmol/mg protein in one of the untreated diabetic rats (group mean±SE = 43±10; N=5), but was < 50 nmol/mg protein in two of the GSH-treated diabetic rats (group mean±SE = 79±17; N=6). When these 11 diabetic rats were subdivided by retinal GSH levels, the low GSH subgroup (<50 nmol/mg; N=6) had decreased a-wave and b-wave amplitudes at the higher end of the scotopic intensities compared to the high GSH subgroup (>50 nmol/mg; N=5), as well as decreased a-wave oscillatory potential amplitudes.

Conclusions: : Retinal GSH is an influential parameter in the investigation of the diabetic rat ERG. Supported by NIH EY017599 (NRH).

Keywords: antioxidants • diabetic retinopathy • electroretinography: non-clinical