Abstract
Purpose: :
The retinal pigmented epithelial (RPE) layer is one of the major areas affected by oxidative stress in ocular diseases. In our study we tested the non-steroidal anti-inflammatory compound (NSAID) sulindac for protection against oxidative stress induced damage in RPE cells. Besides its known anti-inflammatory activity, recent studies have shown that sulindac can protect cardiac cells against oxidative damage by a preconditioning mechanism, independent of its NSAID activity.
Methods: :
The ability of sulindac to protect RPE cells against oxidative stress was determined by treating cultured RPE cells with sulindac, before exposing the cells to oxidative stress or oxygen-glucose deprivation (OGD). Following 48h exposure of the cells to sulindac, RPE cells were exposed to a range of tert-Butyl Hydrogen peroxide (t-BHP) concentrations for 2h to induce oxidative stress. For inducing OGD, RPE cells were added with glucose and serum free media and exposed to less than 0.5% oxygen environment to create in-vitro ischemic conditions. After treatment with t-BHP or OGD cellular viability was determined using the MTT assay.
Results: :
The results show that exposure of cultured RPE cells to oxidative stress using t-BHP or OGD causes significant decrease in cell viability. Pretreatment of RPE cells with sulindac for 48hrs, protects them against both type of insults and enhances survival.
Conclusions: :
In future experiments we plan on showing that the mechanism of protection is unrelated to the NSAID properties of sulindac, and also check for evidence that sulindac is functioning as a chemical preconditioning agent. To do this we will test sulindac sulfone, a known metabolite that is not an NSAID, as well as other known NSAIDS. To better understand the mechanism of protection by sulindac we will evaluate changes in preconditioning markers, the role of ROS scavengers and mitochondrial function. We will also test the protective effect of sulindac against multiple sources of oxidative stress other than t-BHP and OGD. In conclusion we believe that sulindac may represent a novel therapeutic agent to treat ocular diseases that arise from oxidative stress and yield a better understanding of the deleterious affects of ocular oxidative stress.
Keywords: oxidation/oxidative or free radical damage • retinal pigment epithelium • protective mechanisms