Abstract
Purpose: :
To evaluate the effects of resveratrol on the expression of markers for inflammation, oxidative damage, and cellular senescence in primary trabecular meshwork (TM) cells subjected to chronic oxidative stress.
Methods: :
Porcine TM cells where subjected to chronic oxidative stress by incubation in hyperoxic conditions (40% oxygen) for 15 days with resveratrol (25 µM) or vehicle (DMSO) and compared to cells incubated at 5% oxygen. The potential protective effects of resveratrol treatment were evaluated by measurements of the following parameters: expression of inflammatory markers (IL1alpha, IL6, IL8, and ELAM-1), autofluorescence, production of intracellular ROS, senescence associated beta-galactosidase (sa-beta-gal) activity, DNA damage, proteasome activity, protein carbonilation, cell proliferation, and apoptosis.
Results: :
Treatment with resveratrol effectively prevented the increased production of iROS as well as the upregulation of inflammatory markers IL1alpha, IL6, IL8, and ELAM-1 after chronic oxidative stress. Resveratrol treatment also resulted in reduced expression of the senescence markers sa-beta-gal, lipofucsin and carbonilated proteins. Furthermore, resveratrol exerted antiapoptotic effects in an acute oxidative stress model. These effects were not associated with a decrease in cell proliferation.
Conclusions: :
The inhibition of iROS production by resveratrol may help to prevent the induction of inflammatory and senescence markers in TM cells after chronic oxidative stress. These results together with the observed anti-apoptotic effects suggest that resveratrol could potentially have a novel therapeutic role in preventing the TM tissue abnormalities observed in POAG.
Keywords: trabecular meshwork • oxidation/oxidative or free radical damage • drug toxicity/drug effects