Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong, Shantou 515041, China.
Shantou University Medical College, Shantou 515041, China.
Biomolecules. 2024 Mar 5;14(3):307. doi: 10.3390/biom14030307.
: to determine the metabolomics profiles in the plasma samples of primary open-angle glaucoma (POAG) patients. : The plasma samples from 20 POAG patients under intraocular pressure (IOP)-lowering medication treatment and 20 control subjects were subjected to the untargeted metabolomics analysis, among which 10 POAG patients and 10 control subjects were further subjected to the oxylipin-targeted metabolomics analysis by liquid chromatography-mass spectrometry analysis. The prediction accuracy of the differentially abundant metabolites was assessed by the receiver operating characteristic curves. Pathway analysis and correlation analysis on the differentially abundant metabolites and clinical and biochemical parameters were also conducted. : Untargeted metabolomics profiling identified 33 differentially abundant metabolites in the POAG patients, in which the metabolism of linoleic acid, α-linolenic acid, phenylalanine, and tricarboxylic acid cycle were enriched. The correlation analysis indicated that the differentially abundant metabolites were associated with central corneal thickness, peripapillary retinal nerve fiber layer thickness, visual field defects, and lymphocytes. The oxylipin-targeted metabolomics analysis identified 15-keto-Prostaglandin F2 alpha, 13,14-Dihydro-15-keto-prostaglandin D2, 11-Dehydro-thromboxane B2, 8,9-Epoxyeicosatrienoic acid, and arachidonic acid to be significantly decreased in the POAG patients and enriched in the arachidonic acid (AA) pathway. : This study revealed that the metabolites in the arachidonic acid metabolism pathway are differentially abundant, suggesting high IOP may not be the only detrimental factor for optic nerve cell damage in this group of POAG patients. Lipid metabolism instability-mediated alterations in oxylipins and AA pathways may be important in POAG, suggesting that oxidative stress and immune-related inflammation could be valuable directions for future therapeutic strategies.
:旨在确定原发性开角型青光眼(POAG)患者血浆样本中的代谢组学特征。:对 20 名接受降眼压药物治疗的 POAG 患者和 20 名对照者的血浆样本进行了非靶向代谢组学分析,其中 10 名 POAG 患者和 10 名对照者进一步进行了基于液相色谱-质谱分析的氧化应激产物靶向代谢组学分析。采用受试者工作特征曲线评估差异丰度代谢物的预测准确性。还对差异丰度代谢物与临床和生化参数进行了通路分析和相关性分析。:非靶向代谢组学分析鉴定出 POAG 患者中 33 种差异丰度代谢物,其中亚油酸、α-亚麻酸、苯丙氨酸和三羧酸循环代谢物富集。相关性分析表明,差异丰度代谢物与中央角膜厚度、视盘周围视网膜神经纤维层厚度、视野缺损和淋巴细胞有关。氧化应激产物靶向代谢组学分析发现,15-酮基前列腺素 F2α、13,14-二氢-15-酮基前列腺素 D2、11-脱氢血栓烷 B2、8,9-环氧二十碳三烯酸和花生四烯酸在 POAG 患者中显著降低,并在花生四烯酸(AA)途径中富集。:本研究表明,AA 代谢途径中的代谢物存在差异丰度,提示高眼压可能不是这组 POAG 患者视神经细胞损伤的唯一有害因素。脂质代谢不稳定介导的氧化应激产物和 AA 途径改变可能在 POAG 中起重要作用,提示氧化应激和免疫相关炎症可能是未来治疗策略的有价值方向。