Jiang Yaping, Yang Chuanxi, Zheng Yuxiang, Liu Yining, Chen Yihui
Department of Ophthalmology, Yangpu Hospital, Tongji University School of Medicine, Shanghai, China.
Department of Cardiology, Jiangsu Province Hospital, Medical School of Southeast University, Nanjing, China.
Front Cell Dev Biol. 2020 Jun 8;8:344. doi: 10.3389/fcell.2020.00344. eCollection 2020.
We used ultraperformance liquid chromatography coupled with quadrupole/time-of-flight tandem mass spectrometry (UPLC-Q/TOF-MS/MS) to analyze the metabolic profile of reflex tears obtained from patients with dry eye disorders.
We performed a cross-sectional study involving 113 subjects: 85 patients diagnosed with dry eye syndrome (dry eye group) and 28 healthy volunteers (control group). Reflex tears (20-30 μl) were collected from the tear meniscus of both eyes of each subject using a Schirmer I test strip. MS data were acquired with a standard workflow by UPLC-Q/TOF-MS/MS. Metabolites were quantitatively analyzed and matched with entries in the Metlin, Massbank, and HMDB databases. Least absolute shrinkage and selection operator (LASSO) regression was conducted to detect important metabolites. Multiple logistic regression was used to identify the significant metabolic biomarker candidates for dry eye syndrome. Open database sources, including the Kyoto Encyclopedia of Genes and Genomes and MetaboAnalyst, were used to identify metabolic pathways.
After the LASSO regression and multiple logistic regression analysis, 4 of 20 metabolic biomarker candidates were significantly correlated with Ocular Surface Disease Index score, 42 of 57 with fluorescein breakup time, and 26 of 57 with fluorescein staining. By focusing on the overlap of these three sets, 48 of 51 metabolites contributed to the incidence of dry eye and there were obvious changes in different age groups. Metabolic pathway analysis revealed that the main pathways were glucose metabolism, amino acid metabolism, and glutathione metabolism.
Dry eye syndrome induces changes in the metabolic profile of tears, and the trend differs with age. This evidence reveals the relationship between changes in metabolites, symptoms of dry eye syndrome, and age.
我们采用超高效液相色谱-四极杆/飞行时间串联质谱联用技术（UPLC-Q/TOF-MS/MS）分析干眼疾病患者反射性泪液的代谢谱。
我们进行了一项横断面研究，涉及113名受试者：85名被诊断为干眼综合征的患者（干眼组）和28名健康志愿者（对照组）。使用Schirmer I试纸从每个受试者双眼的泪液弯月面收集20-30微升反射性泪液。通过UPLC-Q/TOF-MS/MS采用标准工作流程获取质谱数据。对代谢物进行定量分析，并与Metlin、Massbank和HMDB数据库中的条目进行匹配。进行最小绝对收缩和选择算子（LASSO）回归以检测重要代谢物。采用多因素逻辑回归来识别干眼综合征的重要代谢生物标志物候选物。利用包括京都基因与基因组百科全书和MetaboAnalyst在内的开放数据库来源来识别代谢途径。
经过LASSO回归和多因素逻辑回归分析，20种代谢生物标志物候选物中有4种与眼表疾病指数评分显著相关，57种中有42种与荧光素破裂时间相关，57种中有26种与荧光素染色相关。通过关注这三组的重叠部分，51种代谢物中有48种与干眼的发生有关，并且在不同年龄组中有明显变化。代谢途径分析表明，主要途径为葡萄糖代谢、氨基酸代谢和谷胱甘肽代谢。
干眼综合征会导致泪液代谢谱发生变化，且这种趋势因年龄而异。这一证据揭示了代谢物变化、干眼综合征症状和年龄之间的关系。
