Abstract
Purpose :
Reactive oxygen species (ROS)-induced damage to the retina has been implicated as one of the contributing factors in the pathogenesis of vision-impairing diseases such as diabetic retinopathy (DR) and age-related macular degeneration (AMD). It is hypothesized that certain nutraceutical antioxidants such as caffeine will be effective in preventing metabolic aberrations induced by ROS in the neural retina. This hypothesis is based on our previous studies demonstrating its effectiveness in preventing oxidative damage to the lens and cataract formation, as well as in protecting the neural retina against UV-A induced biochemical and morphological deterioration.
Methods :
Bovine retinas were incubated in medium 199 at 37 degrees C for 6 hours. Xanthine (XA)-xanthine oxidase (XO) were used to generate ROS. Incubations were conducted in 3 groups, controls (medium 199 + 0.5mM XA), experimental (medium 199 + XA+ XO), and caffeine group (medium 199 + XA + XO+ 5mM caffeine). Post-incubation retinas were processed for determining protein, lactate and pyruvate concentrations.
Results :
Lactate concentration in the controls was 2.62±0.43mM/mg protein, while it decreased to 1.04±0.3 mM/mg protein in the presence of XA-XO. Its level in the caffeine group was significantly higher, 2.44±0.65 mM/mg protein, close to the controls. Pyruvate concentration in the control was 0.16±0.05mM/mg protein. It declined significantly with XA-XO to 0.066±0.02 mM/mg protein. Such decrease was substantially prevented by caffeine, pyruvate level in this group being 0.156±0.03mM/mg protein.
Conclusions :
Results clearly demonstrate that incubation of neural retina with XA-XO, a source of ROS, induces inhibition of aerobic as well as anaerobic glycolysis reflected in the decrease in the level of pyruvate and lactate levels, respectively. Caffeine was found to be highly effective in preventing such inhibition, due to its ability to scavenge ROS and thereby prevent inactivation of key glycolytic enzymes. Such effect of caffeine in maintaining metabolism of the neural retina exposed to ROS has been shown for the first time.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.