Abstract
Purpose To determine the association between plasma 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels, a marker for oxidative DNA damage, and patients with primary open-angle glaucoma (POAG) or its clinical phenotypes. Furthermore, we also examined the utility of plasma 8-OHdG as a potential biomarker in POAG. Materials and Methods In a retrospective case-control study, plasma samples were obtained from 50 POAG cases and 45 glaucoma-free controls matched for age, sex, and ethnicity. 8-OHdG levels were measured in duplicate using an enzyme-linked immunosorbent assay (ELISA) on an automated ELISA analyzer. Results There was no significant difference in age, sex, and systemic disease distribution between POAG cases and controls. Both mean and median 8-OHdG levels were significantly elevated in POAG cases and male subjects. The area under the receiver operating characteristic (ROC) curve value for plasma 8-OHdG was 0.653 (95% confidence interval = 0.54–0.76, p = 0.010). The cutoff values based on quartile distribution and ROC curve analysis showed that elevated plasma 8-OHdG significantly increased the risk of POAG by more than 4-folds. Plasma 8-OHdG had a sensitivity of 78% and specificity of 53%. In logistic regression analysis, 8-OHdG showed a significant effect on POAG outcome (p = 0.016) independent of age, sex, smoking, and systemic diseases. However, no significant correlation was observed between 8-OHdG and specific clinical markers of glaucoma such as intraocular pressure (p = 0.699), cup/disc ratio (p = 0.213), and the number of antiglaucoma medications (p = 0.603). Conclusion The study shows that there is a significant association between elevated plasma 8-OHdG and POAG, supporting the role of systemic oxidative stress-induced DNA damage in POAG pathogenesis. However, with a high rate of false-positivity, plasma 8-OHdG may lack the ability to serve as a potential biomarker in POAG. Further studies in a much larger cohort are needed to confirm these findings.
Highlights
Glaucoma is a multifactorial and complex neurodegenerative disease that is caused by gradual apoptosis of retinal ganglion cells (RGCs) and the optic nerve head leading to irreversible blindness [1]
Oxidative stress is believed to be majorly responsible for inducing molecular damage in the anterior chamber of the eye that may result in increased intraocular pressure (IOP) and subsequent manifestation of glaucoma [2]
In a small study consisting of primary open-angle glaucoma (POAG) and pseudoexfoliation glaucoma (PXG), both aqueous humor (AH) and serum samples were elevated in cases compared to controls [17]
Summary
Glaucoma is a multifactorial and complex neurodegenerative disease that is caused by gradual apoptosis of retinal ganglion cells (RGCs) and the optic nerve head leading to irreversible blindness [1]. One of the pathologic mechanisms that may trigger apoptosis is oxidative stress via mitochondrial or endothelial damage, inflammation, and hypoxia [2]. Oxidative stress is believed to be majorly responsible for inducing molecular damage in the anterior chamber of the eye that may result in increased intraocular pressure (IOP) and subsequent manifestation of glaucoma [2]. E oxidative stress is generally induced by excessive generation of reactive oxygen species (ROS), mitochondrial dysfunction, impaired antioxidative defense mechanism, or a combination of these systems [2]. Excessive production of ROS in the cells may induce oxidative damage in the DNA, RNA, mitochondria, and other biomolecules, resulting in impairment of their cellular function(s) or cell death [2, 3]
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