@article{Dong2025, 
author = {Min Dong and Ning-Zhi Zhang and Wen-Ye Cao and Xiao-Xi Deng and Wen-Xi Zhang and Yi-Qiao Xing and Ning Yang},
title = {Assessment of causality between circulating inflammatory proteins and subtypes of diabetic retinopathy},
year = {2025},
journal = {International Journal of Ophthalmology},
volume = {18},
number = {10},
pages = {1971-1979},
keywords = {Mendelian randomization, circulating inflammatory proteins, background diabetic retinopathy, proliferative diabetic retinopathy},
url = {https://www.sciopen.com/article/10.18240/ijo.2025.10.22},
doi = {10.18240/ijo.2025.10.22},
abstract = {AIMTo explore the causal links among circulating inflammatory proteins (CIPs) and the varying severities of diabetic retinopathy (DR).METHODSThis research utilized a two sample Mendelian randomization (MR) approach to explore the causal relationships between 91 CIPs and various severities of DR: background DR (BDR) or non-proliferative DR (NPDR), and proliferative DR (PDR). Single-nucleotide polymorphisms (SNPs) related to the 91 CIPs as exposure factors were identified. These SNPs were selected from an extensive genome-wide association study (GWAS) analyzing large genomic datasets. Genetic variation data of various DR phenotypes provided by the FinnGen collaboration were utilized as outcomes. Inverse-variance weighting (IVW) was used as the main MR analysis. Robustness of study results was evaluated through a series of sensitivity analyses, employing the MR-pleiotropy-test and mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) to confirm the absence of pleiotropy.RESULTSIn a bidirectional MR analysis, we uncovered a complex relationship between CIPs and DR. Elevated levels of tumor necrosis factor ligand superfamily member 14 (TNFSF14), latency associated peptide transforming growth factors beta-1 (LAP-TGF-beta1), interleukin-10 (IL-10), and vascular endothelial growth factor A (VEGF-A) were associated with a reduced risk of NPDR. Conversely, elevated levels of fibroblast growth factor 23 (FGF-23) were associated with an increased risk of NPDR. Concentrations of adenosine deaminase (ADA), matrix metalloproteinase-10 (MMP-10), eotaxin, and IL-10 showed elevated levels and were linked to a reduced risk of NPDR. On the other hand, the levels of oncostatin-M, beta-nerve growth factor (β-NGF), and interleukin-7 (IL-7) were elevated and associated with an increased risk of SNPDR. Elevated levels of ADA, MMP-10, and macrophage colony-stimulating factor 1 (CSF1) were linked to a lower likelihood of PDR. Conversely, elevated levels of Caspase 8 and glial cell line-derived neurotrophic factor (GDNF) were associated with an increased risk of PDR. In reverse MR analysis, DR affected the expression of these factors.CONCLUSIONOur research demonstrates evidence supporting a potential causal link between key inflammatory factors and the risk and prognosis of various DR phenotypes. These findings emphasize the regulation of inflammatory factors responses as a strategic approach for preventing and managing DR. Altogether, our results validate the pathogenic role of inflammatory factors dysregulation in DR and support the rationale for exploring immunotherapeutic targets further.}
}