Immune cells in diabetic retinopathy: A Mendelian randomization study.

The role of immune cells in diabetic retinopathy (DR) is unclear. This study aims to assess the causal effect of various immune cells on DR by Mendelian randomization (MR). Immune cell datasets were acquired from European Bioinformatics Institute, and a DR dataset was acquired in FinnGen. Single nucleotide polymorphisms were screened stepwise according to the assumptions of association, independence, and exclusivity. Inverse variance weighted was used as the main method for MR analysis. MR-Egger was used to assess the horizontal pleiotropy of the results. Cochran Q and leave-one-out methods were respectively used for heterogeneity and sensitivity of the results. MR analysis identified 11 immune cell phenotypes associated with an increased genetic susceptibility to DR: T cell related phenotypes included CD4 on resting Treg, CD4/CD8br, CD28+ CD45RA- CD8dim AC, and CD28- CD25++ CD8br %T cell; NKT cell related phenotypes included CD8br NKT AC and CD3 on NKT; Dendritic cell related phenotypes included CD80 on plasmacytoid DC, CD62L+ plasmacytoid DC, and myeloid DC; The monocyte related phenotype was HLA DR on CD33br HLA DR+ CD14-; and the myeloid cell related phenotype was CD33- HLA DR- AC. No horizontal pleiotropy was observed (P ≥ .05). Cochran Q showed no heterogeneity in the results except for CD8br NKT AC (P < .001) and HLA DR on CD33br HLA DR+ CD14- (P = .002). Sensitivity analysis showed the results were robust. The MR analysis revealed 11 immune cell phenotypes associated with an increased genetic susceptibility to DR. These findings provide a new perspective on the pathogenesis and drug development of DR.