Zhao Tantai, Li Jiani, Wang Yanbin, Guo Xiaojian, Sun Yun
Department of Ophthalmology, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Hunan Clinical Research Center of Ophthalmic Disease, Changsha, Hunan, China.
Heliyon. 2023 Sep 21;9(10):e20329. doi: 10.1016/j.heliyon.2023.e20329. eCollection 2023 Oct.
Age-related macular degeneration (AMD) causes irreversible vision-loss among the elderly in industrial countries. Neovascular AMD (nAMD), which refers to late-stage AMD, is characterized by severe vision-threatening choroidal neovascularization (CNV). Herein, we constructed a global metabolic network of nAMD, based on untargeted metabolomic and lipidomic analysis of plasma samples collected from sixty subjects (30 nAMD patients and 30 age-matched controls). Among the nAMD and control groups, 62 and 44 significantly different metabolites were detected in the positive and negative ion modes, respectively. Grouping analysis further showed that lipid and lipid-like molecule-based superclasses contained the highest number of significantly different metabolites. Lipidomic analysis revealed that 53 lipids among the nAMD and control groups differed significantly; these belonged to four major lipid categories (glycerophospholipids, sphingolipids, glycerolipids, and fatty acids). A discriminative biomarker panel comprising 16 metabolites and lipids, which was constructed using multivariate statistical machine learning methods, could effectively identify nAMD cases. Among these 16 compounds, eight were lipids that belonged to three lipid categories (glycerophospholipids, sphingolipids, and prenol lipids). The top three biomarkers with the highest importance scores were all lipids (a glycerophospholipid and two sphingolipids), highlighting the crucial role played by glycerophospholipid and sphingolipid pathways in nAMD. These differences between the metabolic and lipid profiles of nAMD patients and elderly individuals without AMD provide a readout of the overall metabolic status of nAMD. Further insights into the identified discriminative biomarkers may pave the way for future diagnostic and therapeutic interventions for nAMD.
年龄相关性黄斑变性（AMD）在工业化国家的老年人中会导致不可逆的视力丧失。新生血管性AMD（nAMD），即晚期AMD，其特征是存在严重威胁视力的脉络膜新生血管（CNV）。在此，我们基于对60名受试者（30名nAMD患者和30名年龄匹配的对照）采集的血浆样本进行的非靶向代谢组学和脂质组学分析，构建了nAMD的全球代谢网络。在nAMD组和对照组中，分别在正离子模式和负离子模式下检测到62种和44种显著不同的代谢物。分组分析进一步表明，基于脂质和类脂分子的超类包含的显著不同代谢物数量最多。脂质组学分析显示，nAMD组和对照组中有53种脂质存在显著差异；这些脂质属于四大类脂质（甘油磷脂、鞘脂、甘油酯和脂肪酸）。使用多变量统计机器学习方法构建的一个由16种代谢物和脂质组成的鉴别生物标志物组能够有效识别nAMD病例。在这16种化合物中，有8种是脂质，属于三类脂质（甘油磷脂、鞘脂和异戊二烯醇脂质）。重要性得分最高的前三种生物标志物均为脂质（一种甘油磷脂和两种鞘脂），突出了甘油磷脂和鞘脂途径在nAMD中所起的关键作用。nAMD患者与无AMD的老年人在代谢和脂质谱方面的这些差异反映了nAMD的整体代谢状态。对已鉴定的鉴别生物标志物的进一步深入了解可能为nAMD未来的诊断和治疗干预铺平道路。
