The causal effect of oxidative stress on the risk of glaucoma

Ronghua Shi; Yaxuan Wu; He Chen; Zicheng Zhang; Siqi Bao; Jia Qu; Meng Zhou

doi:10.1016/j.heliyon.2024.e24852

The causal effect of oxidative stress on the risk of glaucoma

Heliyon. 2024 Jan 17;10(3):e24852. doi: 10.1016/j.heliyon.2024.e24852. eCollection 2024 Feb 15.

Authors

Ronghua Shi^{1

2}, Yaxuan Wu^{1

2}, He Chen^{1

2}, Zicheng Zhang^{1

3

2}, Siqi Bao^{1

3

2}, Jia Qu^{1

3

2}, Meng Zhou³

Affiliations

¹ School of Biomedical Engineering, School of Information and Communication Engineering, Hainan University, Haikou 570228, China.
² Hainan Institute of Real World Data, Qionghai, 571437, China.
³ National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China.

Abstract

Glaucoma is a complex multifactorial disease. Oxidative stress has been implicated in its pathogenesis. However, establishing a causal relationship between oxidative stress and glaucoma is challenging due to confounding and reverse causality. In this study, we performed bidirectional two-sample Mendelian randomization (MR) analyses based on genetic instrumental variables as proxies for 11 biomarkers of oxidative stress injury to investigate the causal relationship between oxidative stress and glaucoma. Eight significant associations were identified. Increased circulating levels of catalase (OR = 0.915, 95 % CI: 0.848-0.987, P = 0.022), retinol (OR = 0.481, 95 % CI: 0.248-0.932, P = 0.044) and superoxide dismutase (OR = 0.779, 95 % CI: 0. 616-0.986, P = 0.038) are associated with a decreased risk of glaucoma, whereas an increased myeloperoxidase level (OR = 2.145, 95 % CI: 1.119-4.111, P = 0.029) is associated with an increased risk of glaucoma. Glaucoma was causally associated with lower levels of total bilirubin (OR = 0.961, 95 % CI: 0.927-0.997, P = 0.039), glutathione peroxidase (OR = 0. 934, 95 % CI: 0.890-0.981, P = 0.006), paraoxonase (OR = 0.883, 95 % CI: 0.810-0.963, P = 0.005) and albumin (OR = 0.988, 95 % CI: 0.978-0.998, P = 0.014). The bidirectional MR analysis revealed a causal relationship between oxidative stress and glaucoma. These findings provide a greater understanding of the underlying mechanisms of glaucomatous neurodegeneration and imply a potential therapeutic approach for glaucoma through targeting oxidative stress pathways.

Keywords: Glaucoma; Mendelian randomization study; Oxidative stress.