早发性白内障与年龄相关性白内障患者房水代谢组学的差异研究  

Differential analysis of aqueous humor metabolomics between presenile cataract and senile cataract

作　　者：陈曦腾 高楠 寇振宇 吴桂佳 蒋元丰 杨军 白小妹 东莉洁[1] 田芳 Chen Xiteng;Gao Nan;Kou Zhenyu;Wu Guijia;Jiang Yuanfeng;Yang Jun;Bai Xiaomei;Dong Lijie;Tian Fang(Tianjin Key Laboratory of Retinal Functions and Diseases,Tianjin Branch of National Clinical Research Center for Ocular Disease,Eye Institute and School of Optometry,Tianjin Medical University Eye Hospital,Tianjin 300384,China)

机构地区：[1]天津医科大学眼科医院、天津医科大学眼视光学院、天津医科大学眼科研究所、国家眼耳鼻喉疾病临床医学研究中心天津市分中心、天津市视网膜功能与疾病重点实验室,天津300384

出　　处：《中华眼科杂志》2024年第6期518-527,共10页Chinese Journal of Ophthalmology

基　　金：国家自然科学基金(81900846);天津市医学重点学科(专科)建设项目(TJYXZDXK-037A)。

摘　　要：目的:探讨早发性白内障与年龄相关性白内障患者房水中代谢物及代谢通路的差异。方法:代谢组学研究。收集2020年8月至2022年9月就诊于天津医科大学眼科医院的16例(17只眼)白内障患者。其中早发性白内障8例(8只眼),年龄相关性白内障8例(9只眼)。收集患者年龄、性别、术前裸眼视力、眼压、晶状体功能失调指数和眼轴长度等一般临床资料,并于白内障摘除术中留取房水和前囊膜组织标本,采用液相色谱-串联质谱法非靶向检测房水中的代谢物,进一步使用主成分分析、差异分析、聚类分析、相关性分析筛选差异代谢物,并根据代谢物的变化倍数(FC)对差异代谢物进行排名。使用受试者工作特征(ROC)曲线分析和代谢富集分析来筛选两组间的差异通路,并鉴定早发性白内障的生物标志物。前囊膜组织行免疫组织化学染色。采用比色法检测丙酮酸含量验证代谢组学分析结果。结果:8例早发性白内障患者中男性7例,女性1例,年龄(37.50±4.90)岁;8例年龄相关性白内障患者中男性7例,女性1例,年龄(73.44±5.22)岁;基线资料除年龄外差异均无统计学意义(P>0.05)。差异分析共鉴别出347种差异代谢物,其中10种经ROC曲线分析确定为潜在的早发性白内障生物标志物(均P<0.05),其中阳离子(POS)模式5种,分别是丙氧卡因(log 2FC=7.26)、2-甲基-2,3,4,5-四氢-1,5-苯并氧氮杂卓-4-酮(log 2FC=6.35)、l-焦谷氨酸(log 2FC=-1.72)、亮氨酰脯氨酸(log 2FC=-0.77)和胆碱(log 2FC=-0.56),阴离子(NEG)模式5种,分别是N-苯乙酰谷氨酰胺(log 2FC=-1.84)、丙酮酸(log 2FC=1.07)、抗坏血酸(log 2FC=0.92)、假尿嘧啶核苷(log 2FC=-0.68)和棕榈酸(log 2FC=-0.51)。代谢富集分析共富集到72条差异通路(POS模式32条,NEG模式40条),其中谷胱甘肽代谢及半胱氨酸和蛋氨酸代谢、糖酵解或糖异生、丙酮酸代谢、三羧酸循环两组间的差异有统计学意义(P<0.05)。验证�Objective To explore the differences in metabolites and metabolic pathways in the aqueous humor between patients with presenile cataracts and senile cataracts.Methods This metabolomic study was conducted at Tianjin Medical University Eye Hospital from August 2020 to September 2022.Eight patients with presenile cataracts(8 eyes)and 8 patients with senile cataracts(9 eyes)were included.Data were collected,including age,gender,preoperative uncorrected visual acuity,intraocular pressure,lens dysfunction index,and axial length.Aqueous humor and anterior capsule tissue samples were obtained during cataract surgery.Metabolites in the aqueous humor were detected using Liquid Chromatography-Mass Spectrometry in a non-targeted approach.The principal component analysis,differential analysis,clustering analysis,and correlation analysis were performed to identify differentially expressed metabolites.These metabolites were ranked based on the fold change(FC).The receiver operating characteristic(ROC)curve analysis and metabolic enrichment analysis were used to identify differential pathways and potential biomarkers for presenile cataracts.Immunohistochemistry was conducted on anterior capsule tissues,and pyruvate levels were measured by colorimetry to validate metabolomic results.Results Patients with presenile cataracts included 7 males and 1 female,with a mean age of(37.50±4.90)years.Patients with senile cataracts were 7 males and 1 female,with a mean age of(73.44±5.22)years.Except for age,there were no significant differences in baseline data(P>0.05).A total of 347 differential metabolites were identified,10 of which were potential biomarkers for presenile cataract according to the ROC curve analysis(all P<0.05),including propoxycaine(log2FC=7.26),2-methyl-2,3,4,5-tetrahydro-1,5-benzodiazepine-4-ketone(log2FC=6.35),l-pyroglutamic acid(log2FC=-1.72),leanly-proline(log2FC=-0.77),and choline(log2FC=-0.56)in the positive ion mode,and N-phenylacetyl glutamine(log2FC=-1.84),pyruvate(log2FC=1.07),ascorbic acid(log2FC=0.92),pseud

关 键 词：白内障 眼房水 代谢组学 生物标记 计算生物学 

分 类 号：R776.1[医药卫生—眼科]