Redox State of Glutathione in Smokers Versus Nonsmokers as a Potential Indicator of AMD Susceptibility

Abstract

Abstract: : Purpose: To measure blood plasma glutathione status in smokers versus nonsmokers. Smoking is a risk factor for age-related macular degeneration (AMD). Smoking produces harmful reactive oxygen species (ROS) which can lead to a state of oxidative stress. Glutathione, a major antioxidant is important in protecting the body against oxidative stress. The extent of oxidation of GSH, expressed as the redox state, may be an important indicator of degenerative aging diseases such as AMD. Methods: Measurements of plasma gluthathione (GSH) and glutathione disulfide (GSSG) were obtained from volunteer smokers and nonsmokers between the ages of 45-93 years (n=122 nonsmokers, n=50 smokers). The redox potentials (E_h) of the different thiol/disulfide pools were calculated using the Nernst equation. Results: The blood plasma redox state in smokers was -127±19 mV, which was significantly more oxidized compared to nonsmokers, which was -135±18 mV(p<0.01). The mean concentration of glutathione in smokers was 1.8±1.2mM which was significantly lower than nonsmokers, which was 2.3±1.0 mM (p<0.001). The mean age for smokers was 60±8 years and the mean for nonsmokers was 68±11 years. Conclusions: Smokers demonstrate a significantly more oxidized blood plasma glutathione redox status than nonsmokers, suggesting that tissues in smokers, including the retina and RPE, may be subjected to greater oxidative stress. Blood plasma redox status may be a good marker for AMD susceptibility. The RPE, already under high oxidative stress due to focused light, high oxygen concentration, and lipid peroxidation, may be even more sensitive to a shift in redox caused by smoking. This extra oxidative stress may contribute to the onset and progression of age-related macular degeneration (AMD) and be a factor in the link between smoking and increased risk of AMD.

Keywords: oxidation/oxidative or free radical damage • age-related macular degeneration • aging