Inhibition of glycolysis in the retina by oxidative stress: prevention by pyruvate

Abstract

Intraocular generation of reactive oxygen species (ROS) with consequent oxidative stress has been shown to be a significant factor in the pathogenesis of many vision-impairing diseases such as cataracts and retinal degenerations. Previous studies have shown that pyruvate can inhibit such oxidative stress. This is attributable to its property of scavenging various ROS and consequently inhibiting many of the apparent toxic reactions such as lipid peroxidation and loss of tissue thiols. It is hence expected that ROS will have an adverse effect on tissue metabolism also. The present investigations were hence undertaken to study the possibility that while scavenging ROS, the compound could be effective also in preventing the inhibition of tissue metabolism as well. Since glycolysis constitutes the major bioenergetic source of the retina, the objective of the present studies was to ascertain if the effects of pyruvate are indeed reflected in the maintenance of this pathway even when the tissue is exposed to ROS. This hypothesis was examined by incubating retinal explants in ROS-generating medium in the absence and presence of pyruvate and measuring ³H₂O generated from 5-³H glucose. In addition, the lactate generated was also measured. As hypothesized, ROS-induced inhibition of glycolysis indexed by the decrease in ³H₂O as well as lactate formation was significantly prevented by pyruvate. This effect was also reflected by the elevation of NAD/NADH ratio, a major pacemaker of glycolysis.