Metabolomic Profiling of the Aqueous Humor in Patients with Wet Age-Related Macular Degeneration Using UHPLC-MS/MS
Metabolomic Profiling of the Aqueous Humor in Patients with Wet Age-Related Macular Degeneration Using UHPLC-MS/MS
复制标题
使用 UHPLC-MS/MS 对湿性年龄相关性黄斑变性患者的房水进行代谢组学分析
DOI：
10.1021/acs.jproteome.0c00036
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发表时间：
2020-06-05
影响因子：
4.4
通讯作者：
Chu, Yanhua
中科院分区：
文献类型：
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作者：
Han, Guoge;Wei, Pinghui;Chu, Yanhua
评估年龄相关性黄斑变性（AMD）的代谢组学改变可以深入了解其发病机制。我们比较了湿性AMD患者（n = 26）和年龄和性别匹配的无AMD白内障手术患者（n = 20）的房水代谢谱。采用超高效液相色谱串联质谱法进行了一项全球非靶向代谢组学研究。错误发现校正后的单变量分析显示，在测量的291种代谢物中，有18种代谢物发生了显著改变。这些差异代谢组学特征指出了三种相互关联的代谢途径：肉毒碱相关线粒体氧化途径受损（肉毒碱，脱氧肉毒碱，N6-三甲基-L-赖氨酸），改变的碳水化合物代谢途径（顺乌头酸、衣康酸和美司匹林酸），其在衰老和免疫中起作用，以及活化的抗衰老保护途径。（甘氨酸甜菜碱，肌酸），其潜在地有助于疾病的发病机制。这些结果表明，AMD的代谢功能障碍是以肾脏为中心的，并可能提供新的见解湿性AMD的病理生理和新的治疗策略。
Assessing metabolomic alterations in age-related macular degeneration (AMD) can provide insights into its pathogenesis. We compared the metabolomic profiles of the aqueous humor between wet AMD patients (n = 26) and age- and sex-matched patients undergoing cataract surgery without AMD as controls (n = 20). A global untargeted metabolomics study was performed using ultra-high-performance liquid chromatography tandem mass spectrometry. Univariate analysis after the false discovery correction showed 18 significantly altered metabolites among the 291 metabolites measured. These differential metabolomic profiles pointed to three interconnected metabolic pathways: a compromised carnitine-associated mitochondrial oxidation pathway (carnitine, deoxycarnitine, N6-trimethyl-L-lysine), an altered carbohydrate metabolism pathway (cis-aconitic acid, itaconatic acid, and mesaconic acid), which plays a role in senescence and immunity, and an activated osmoprotection pathway (glycine betaine, creatine), which potentially contributes to the pathogenesis of the disease. These results suggested that metabolic dysfunction in AMD is mitochondrial-centered and may provide new insights into the pathophysiology of wet AMD and novel therapeutic strategies.