Exploring the effect of immune cells in retinal ischemia-reperfusion injury based on Mendelian randomization and colocalization analysis_Chinese Journal of Ocular Fundus Diseases

Authors：

Wang Wenting ^1,2 , Liang Na ^1,2 , Ha Wenjing ² ,  Peng Shaomin ¹

1. ;
2. ;

Corresponding author：

Peng Shaomin, Email: pengshaomin@ahmu.edu.cn

Keywords：

Retinal ischemia-reperfusion injury; Immune cell phenotype; Mendelian randomization; Colocalization analysis

DOI：

10.3760/cma.j.cn511434-20250320-00121

Video：

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Objective To investigate the potential role of immune cells in retinal ischemia-reperfusion injury (RIRI)-associated diseases, employing Mendelian randomization (MR) and colocalization analysis. Methods Genome-wide association study (GWAS) datasets of immune cells were obtained for conducting two-sample bidirectional MR analysis and colocalization analysis. A total of 731 immune cell phenotypes from the GWAS datasets were selected as exposure variables, and four RIRI-related diseases, namely diabetic retinopathy (DR), primary angle-closure glaucoma (PACG), retinal artery occlusion (RAO), and retinal vein occlusion (RVO), were chosen as outcome variables. The 731 immune cell phenotypes included seven cell types: B cells, classical dendritic cells, T cell maturation stages, monocytes, myeloid cells, TBNK cell group [T cells, B cells, and natural killer cells], and regulatory T cells. The inverse variance weighted (IVW) method was used to assess the causal relationship between immune cell phenotypes and RIRI-related diseases; colocalization analysis was performed to verify the possibility of shared causal variants between immune cell phenotypes and outcomes. Results The IVW method analysis results showed that 117 were related to RIRI. After adjusting the false discovery rate (FDR) (P_FDR＜0.05) and conducting reverse MR analysis, 19, 49, 37, 13, and 9 types of immune cell phenotypes were respectively associated with potential causal relationships with non-proliferative diabetic retinopathy (NPDR), proliferative diabetic retinopathy (PDR), PACG, RAO, and RVO. Among them, in the monocyte group, CD64 on CD14⁺ CD16⁺ monocyte significantly increased the risk of NPDR occurrence [odds ratio (OR)=1.544, 95% confidence interval (CI) 1.184-2.014, P=0.011], and CX3CR1 on monocyte significantly decreased the risk of NPDR occurrence (OR=0.823, 95% CI 0.727-0.933, P=0.012); in the TBNK cell group, CD4⁺ CD8^dim% T cells significantly increased the risk of PACG occurrence (OR=1.262, 95%CI 1.075-1.483, P=0.025), and CD8 on EM CD8⁺ T cells was a risk factor for PACG occurrence (OR=1.156, 95%CI 1.049-1.275, P=0.026). The colocalization analysis results showed that 32 types of immune cell phenotypes had significant common causal variant signals with outcome variables (posterior probability H₄＞0.8), located at 14 gene loci. Five immune cell phenotypes related to B-cell activating factor receptors and PDR were jointly located at the CENPM and TNFRSF13C gene loci. the specific T cell subsets CD45RA^-CD4⁺ T cells and cytotoxic T cell phenotype CD28⁺CD45RA^-CD8^dim T cells (a type of memory CD^8dim T cell) were colocalized with PACG at the PTPRC gene. The CD33 and RVO on myeloid cell phenotype monocyte-like myeloid-derived suppressor cells are jointly located at the CD33 locus (rs3865444) of their encoding gene. Conclusion MR and colocalization analysis results reveal complex genetic causal relationships between multiple immune cell phenotypes and four RIRI-related diseases.

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Chinese Journal of Ocular Fundus Diseases

Latest ArticlesExploring the effect of immune cells in retinal ischemia-reperfusion injury based on Mendelian randomization and colocalization analysis

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