Sun Yuxin, Zhang Ziran, Chen Zejun, Li Zhengran, Wang Zijin, Wu Fanye, Ma Xinyu, Wang Shaoyu, Cao Mingzhe, Yi Guoguo, Fu Min
The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China.
Ophthalmology Department, Zhujiang Hospital Affiliated With Southern Medical University, Guangzhou, China.
J Cell Mol Med. 2025 Jun;29(11):e70614. doi: 10.1111/jcmm.70614.
Although lipid metabolism is a critical factor in the pathogenesis of diabetic retinopathy (DR), the connection between lipidome and DR is still a subject of debate. We aimed to demonstrate that lipidome could serve as novel biomarkers for DR and elucidate the mediating role of inflammatory factors. Data for our investigation are available from the GWAS catalogue and FinnGen Biobank. The bidirectional Mendelian randomization (MR) analyses were conducted to assess the "total effect" between lipidome and DR and its subtypes. Subsequently, the mediation analyses were performed to explore the involvement of circulating inflammatory proteins in mediating the connection between them. Mediation proportion was calculated to measure the contribution of inflammatory factors to the overall effect. Ultimately, a battery of sensitivity tests proceeded to examine the dependability of the findings. This study has revealed a causal relationship between lipidome and different stages of DR. Additionally, we have successfully discovered a range of new lipids that protect against DR and have the potential to serve as new markers. This study also highlights the important role of inflammatory factors in elucidating the protective mechanisms of lipids against DR and provides new perspectives on lipidomic-based treatments and cytokine-targeted interventions for DR.
尽管脂质代谢是糖尿病视网膜病变（DR）发病机制中的一个关键因素，但脂质组与DR之间的联系仍是一个有争议的话题。我们旨在证明脂质组可作为DR的新型生物标志物，并阐明炎症因子的介导作用。我们调查的数据可从全基因组关联研究（GWAS）目录和芬兰生物银行获得。进行双向孟德尔随机化（MR）分析以评估脂质组与DR及其亚型之间的“总体效应”。随后，进行中介分析以探讨循环炎症蛋白在介导它们之间联系中的作用。计算中介比例以衡量炎症因子对总体效应的贡献。最终，进行了一系列敏感性测试以检验研究结果的可靠性。本研究揭示了脂质组与DR不同阶段之间的因果关系。此外，我们成功发现了一系列可预防DR的新脂质，并有可能作为新的标志物。本研究还强调了炎症因子在阐明脂质对DR的保护机制中的重要作用，并为基于脂质组学的DR治疗和细胞因子靶向干预提供了新的视角。
