Serum Iron Status and Retinal Degenerative Diseases: A Mendelian Randomization Study on AMD, RP, and DR

<b>Background</b>: Observational studies have noted that patients with certain retinal degenerative diseases exhibit iron disturbances in the retina or vitreous compared to healthy controls. However, the connection between serum iron status and these diseases remains unclear. This study aims to explore the potential causal relationship between serum iron status biomarkers and the development of age-related macular degeneration (AMD), retinitis pigmentosa (RP), and diabetic retinopathy (DR). <b>Methods</b>: A two-sample Mendelian randomization (MR) analysis was conducted to investigate the causal relationship between serum iron status and several retinal degenerative diseases. Genome-wide association study (GWAS) summary-level data were extracted from public GWAS databases. Inverse-variance weighting (IVW), MR-Egger regressions, Simple model, Weighted median, and Weight mode were used as MR methods. Sensitivity analysis was conducted to confirm the robustness of the results by examining horizontal pleiotropy and heterogeneity through MR-Egger intercept and leave-one-out analysis. <b>Results</b>: The MR analysis revealed causal relationships between genetically predicted serum iron status biomarkers and various retinal diseases. Transferrin was positively associated with the odds of AMD (whether dry or wet) (OR = 1.167, 95% CI = 1.045-1.304, <i>p</i> = 0.006) and wet AMD (OR = 1.194, 95% CI = 1.018-1.402, <i>p</i> = 0.030). Ferritin was negatively associated with the odds of wet AMD (OR = 0.555, 95% CI = 0.333-0.927, <i>p</i> = 0.024). Serum iron (OR = 0.508, 95% CI = 0.260-0.993, <i>p</i> = 0.048) and transferrin saturation (OR = 0.508, 95% CI = 0.260-0.993, <i>p</i> = 0.048) were negatively associated with the odds of RP. <b>Conclusions</b>: These findings provide evidence supporting a potential causal relationship between serum iron status and various retinal degenerative diseases, highlighting a direction for future research into the underlying mechanisms of these diseases.