Lifestyle Modify Optic Nerve Injury in Mendelian Randomization.

Background: Optic nerve injury, as a neurodegenerative disorder, leads to irreversible visual impairment. Although the underlying mechanisms linking physical activity to optic nerve injury remain unclear, this study aimed to establish a causal relationship between physical activity and optic nerve injury using a Mendelian randomization (MR) framework. Methods: This MR study utilized genome-wide significant variants as instrumental variables (IVs) for assessing the relationship between physical activity and optic nerve injury, focusing on individuals of European descent. The approach was supported by comprehensive sensitivity analyses and augmented by bioinformatics tools including differential gene expression, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Results: Our study demonstrated that after adjustment for MVPA, alcohol intake, BMI, blood glucose, blood lipids, and smoking, LST was positively associated with glaucoma risk (β = 0.016, 95% CI: 0.004 to 0.027, p = 0.014), indicating its role as an independent risk factor. Conversely, MVPA was negatively associated with glaucoma risk (β = -0.012, 95% CI: -0.022 to -0.002, p = 0.026), supporting a protective effect, while smoking also showed a significant association (β = -0.020, 95% CI: -0.039 to -0.002, p = 0.037). Sensitivity analyses confirmed the robustness of these findings, and bioinformatic analyses implicated cholesterol metabolism and fibrosis pathways in optic nerve injury. Conclusion: These findings underscore the potential of lifestyle modifications, including increased physical activity and reduced sedentary behavior, as a cost-effective strategy to prevent and manage optic nerve injury.