Thiol and Glutathione Homeostasis Parameters as Plasma Biomarkers of Oxidative Stress in Age-Related Macular Degeneration

Abstract

Purpose: To determine extracellular thiol homeostasis and intracellular glutathione homeostasis as a plasma biomarker for oxidative stress and to compare these parameters in non-exudative/exudative AMD patients and healthy individuals. Method: 30 non-exudative AMD, 28 exudative AMD, and 36 age-matched healthy control subjects enrolled to the study. Extracellular total thiol, native thiol, disulphide amounts and intracellular oxidized/reduced glutathione levels of subjects were determined, and disulphide/thiol and oxidized/reduced glutathione percent ratios were calculated. Results: In comparison with the control group both non-exudative and exudative AMD patients had higher plasma disulfide levels (20.5(4.8) vs. 4(3.1), p<0.001 and 22.5(7.5) vs. 15.4(3.1), p<0.001; respectively) and higher disulphide/thiol (6.64(2.57) vs. 5.4(1.9), p=0,002 and 7.05(3.14) vs. 5.4(1.9), p<0.001; respectively), in addition to higher oxidized glutathione levels (64.6(40.8) vs. 27.3(21.9), p=0.015 and 73.9(44.1) vs. 27.3(21.9), p=0.002; respectively) and oxidized/reduced glutathione ratio(6.48(8.35) vs. 3.14(3.31), p=0,034 and 10.21(10.28) vs. 3.14(3.31), p=0,003; respectively). Although there was no significant difference between groups in term of total thiol (361.5(61.6), 355.1(87.7) and 340.9(72.4), respectively, p=0,585); native thiol (318.8(62.4), 307.1(73.7) and 299.3(79.2), respectively, p=0,382); total reduced glutathione (986.3(282.1), 871.5(271.6) and 881.8(290.9), respectively, p=0.344) and native reduced glutathione (873.4(367.6), 723.7(379.0) and 797.2(307.5), respectively, p=0,113). However, there was no significant difference between non-exudative and exudative AMD groups in terms of both extracellular thiol homeostasis and intracellular glutathione homeostasis. Conclusion: Greater extent of both extracellular disulphide and intracellular oxidized glutathione production occurred in AMD patients compared to age-matched healthy controls indicates the role of increased oxidative stress in AMD development. Further studies are needed to confirm the pathophysiologic role of homeostasis in these buffer systems in AMD.