Xu Weichen, Fan Qinglu, Meng Yang, Nie Zhihao, Sawut Abdulla, Xie Songping, Chen Changzheng
Department of Ophthalmology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, 430060, Hubei Province, China.
Department of Thoracic Surgery, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, 430060, Hubei Province, China.
Sci Rep. 2025 Mar 14;15(1):8876. doi: 10.1038/s41598-025-92153-y.
Glaucoma is a leading cause of irreversible blindness worldwide, with its pathogenesis incompletely understood. Inflammation, as an important aspect of glaucoma, has attracted increasing attention. In this study, we performed a Mendelian randomization (MR) analysis to investigate the association between 91 circulating inflammatory proteins and glaucoma. First, a bidirectional MR was employed to screen for inflammatory proteins that potentially influence glaucoma risk, with the findings further confirmed by a replication sample MR. Then, a mediation analysis was employed to assess the mediating effects of glaucoma endophenotypes on glaucoma. Finally, we performed a subgroup MR to investigate the association between circulating proteins and glaucoma subtypes, including primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG). The bidirectional MR suggested 7 out of the 91 proteins were possibly related with glaucoma risk, with T-cell surface glycoprotein CD5 (CD5) (odds ratio (OR) = 0.87; 95% confidence interval (CI): 0.81-0.94; P = 2.46 × 10) passing false discovery rate correction. This result was verified by the replication sample MR. The mediation analysis revealed that intraocular pressure (IOP) (β=-0.05; 95% CI: -0.02--0.09; P = 1.56 × 10) was a mediator of CD5's protective effect on glaucoma. The subgroup MR indicated that CD5 conferred a protective causal effect specifically on POAG, not PACG. Moreover, IOP served as a mediator in the association between CD5 and POAG, explaining a proportion of 38.29% of CD5's protective effect against POAG. Our findings suggest a negative causal association between circulating CD5 and POAG risk, which is partially mediated by IOP. This indicates that targeted CD5 therapy may be beneficial to POAG eyes.
青光眼是全球不可逆性失明的主要原因，其发病机制尚未完全明确。炎症作为青光眼的一个重要方面，已引起越来越多的关注。在本研究中，我们进行了孟德尔随机化（MR）分析，以探究91种循环炎症蛋白与青光眼之间的关联。首先，采用双向MR筛选可能影响青光眼风险的炎症蛋白，其结果通过重复样本MR进一步证实。然后，进行中介分析以评估青光眼内表型对青光眼的中介作用。最后，我们进行了亚组MR，以研究循环蛋白与青光眼亚型之间的关联，包括原发性开角型青光眼（POAG）和原发性闭角型青光眼（PACG）。双向MR表明，91种蛋白中有7种可能与青光眼风险相关，其中T细胞表面糖蛋白CD5（CD5）（优势比（OR）=0.87；95%置信区间（CI）：0.81 - 0.94；P = 2.46×10）通过了错误发现率校正。该结果经重复样本MR验证。中介分析显示，眼压（IOP）（β=-0.05；95%CI：-0.02 - -0.09；P = 1.56×10）是CD5对青光眼保护作用的中介因素。亚组MR表明，CD5对POAG具有特异性保护因果效应，对PACG则无此作用。此外，IOP在CD5与POAG的关联中起中介作用，解释了CD5对POAG保护作用的38.29%。我们的研究结果表明，循环CD5与POAG风险之间存在负因果关联，且部分由IOP介导。这表明靶向CD5治疗可能对POAG患者有益。
