Prevention of peroxide-induced damage to the neural retina by caffeine
Hegde KR, Brown DD and Varma SD. 2018
Purpose: Oxidative stress is known to be involved in the pathogenesis of several retinal diseases such as diabetic retinopathy, age-related macular degeneration, retinitis pigmentosa, etc. Caffeine, a xanthine alkaloid, is a highly effective scavenger of reactive oxygen intermediates, and has been previously demonstrated to protect the lens against oxidative damage and consequent cataract formation. The primary objective of this study is to examine whether caffeine will be able to protect the neural retina against direct peroxide-induced biochemical stress.
Methods: Neural retinas dissected from bovine eyes enucleated immediately after euthanization were incubated in medium 199 for 4 hours in a humidified incubator at 37ᵒ C maintained at 5% CO2. Peroxide stress was induced by the addition of H2O2 to a final concentration of 9mM. The medium in the caffeine group contained 9mM H2O2 + caffeine (5mM). The control group was incubated without peroxide and caffeine. Post-incubation retinas were processed for determination of water soluble protein concentration using Bradford’s reagent. Biochemical damage was assessed by measurement of glutathione (GSH).
Results: Exposure to H2O2 led to ~40% decrease in the level of GSH in the neural retina as compared to the controls. Addition of caffeine maintained its level to ~95% of the control value. The maintenance of GSH level by caffeine in neural retina exposed to oxidative stress was clearly evident.
Conclusions: The above results suggest that caffeine is significantly effective in preventing biochemical damage to the neural retina subjected to peroxide stress. This is partly attributed to the known oxyradical scavenging effect of caffeine. Additional possible mechanisms of its protective effect, such as the modulation of expression of antioxidant genes and its role in boosting metabolism, are currently being investigated.
Neuroprotective effect of caffeine on retina exposed to oxygen free radicals
Destiny Brown, Erica Monk, Dahlia Copeland, Kavita Hegde
Department of Natural Sciences, Coppin State University, Baltimore, MD 21216
Morgan State University Conference, April 2018
Oxyradical-induced damage to the retina has been implicated in the pathogenesis of vision-impairing diseases such as diabetic retinopathy and age-related macular degeneration. Available treatments are not fully effective in delaying the onset and stopping the progress of retinal damage and the associated vision loss. Hence development of newer therapeutic compounds is necessary. The effectiveness of metabolic and nutritional antioxidants such as pyruvate and caffeine in preventing oxidative damage to the lens has been previously demonstrated. This effect is primarily due to their ability to scavenge reactive oxygen species (ROS) and prevent oxidation of cellular enzymatic and structural proteins, lipids and nucleic acids. The objective here is to determine whether caffeine can protect the neural retina against ROS-induced damage. Fresh bovine neural retinas were incubated in medium 199 in the presence of ROS ± caffeine (5mM). The control group was incubated without ROS & caffeine. Retinas were processed for measuring glutathione (GSH) content. Metabolic status was assessed by measuring lactate concentration. Expression of antioxidant genes was determined by rt-PCR. ROS exposure decreased the GSH content by 40%; caffeine addition prevented such decrease, maintaining GSH closer to the controls. Lactate levels in ROS alone group decreased to 65% of the controls; caffeine group had lactate concentration closer to the controls. Preliminary PCR studies also indicate significant modulation of antioxidant genes expression by ROS and caffeine. Overall, the results suggest that caffeine protects the neural retina from ROS-induced damage, and is hence a promising compound for continued investigations.
Grant support: This project was supported by Elkins Professorship awarded to Dr. Kavita Hegde by University System of Maryland, AY 2016-17 & 2017-18.
Biochemical, morphological and gene expression modulation induced by oxidant challenge to the neutral retina: Possible prevention by pyruvate.
Presented by Ms. Mariah Benjamin
Faculty Mentor: Dr. Kavita Hegde
Coppin State University Fourth Annual Science Symposium
September 22, 2016
Excessive generation of reactive oxygen species (ROS) and consequent oxidative stress has been known to be involved in the pathogenesis of many retinal diseases such as diabetic retinopathy (DR) and age-related macular degeneration (AMD), the two most common vision-impairing and blinding diseases of the retina, especially in Western countries. Although both these diseases have several contributing factors in their pathogenesis, one of the common aberrations seen in both, and several other retinal diseases, is oxidative damage and consequent degeneration of the neural retina with resulting vision loss. Current treatments for these diseases, especially AMD, have limited effectiveness in terms of restoring vision and halting progressive vision loss. It is hence considered necessary to continue to develop newer treatments or novel compounds which have the ability to effectively thwart the degenerative process and preserve useful vision. Studies are currently underway to test the effectiveness of pyruvate, a highly effective scavenger of ROS, in preventing biochemical damage to the neural retina. In addition, further studies are also planned to test whether pyruvate can regulate the redox status of the tissue through modulating the transcription and activity of Nrf2 and the expression of Nrf2 downstream genes in the neural retina when presented with oxidant challenge.
Poster Presentation: Biochemical and Nrf2-inducible Gene Expression Studies in ROS-exposed Retina and their Modulation by Pyruvate
Presented by Chisomaga Madufor
Faculty Mentor: Dr. Kavita Hegde
Morgan State University Undergraduate and Graduate Research Conference
April 13, 2017