Alteration of Tear Metabolomics Profiling in Infants With Retinopathy of Prematurity.

IF 4.7 2区 医学 Q1 OPHTHALMOLOGY
Zixin Fan, Shuo Yang, Xiaofeng Lu, Sifan Zhang, Xianlu Zeng, Lin Lin, Duo Yuan, Jian Zeng, Guoming Zhang
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引用次数: 0

Abstract

Purpose: The purpose of this study was to investigate the characteristics of metabolomic profile in the tears from infants with retinopathy of prematurity (ROP) and further define noninvasive biomarkers.

Methods: This prospective study included 94 eyes from 47 premature infants. Tear samples from 23 infants with ROP (15 treatment-requiring ones [ROP (t)] and 8 non-treatment-requiring ones [ROP (nt)]) and 24 infants without ROP were collected with Schirmer strips after topical anesthesia. Detailed fundus examination upon pupil dilation were conducted, with data on demographics and birth history recorded. Untargeted tear metabolomic analysis based on ultra-performance liquid chromatography-mass spectrometry was performed.

Results: Adjusted by sex, postmenstrual age, gestational age, and birth weight, among 145 metabolites quantified, 3,5-di-tert-butyl-4-hydroxybenzaldehyde, caffeine, and trehalose were identified to be upregulated in the tears from infants with ROP when compared to those from premature infants with non-ROP, whereas uric acid, dihomo-γ-linolenic acid, nootkatone, pyridoxal, ornithine, 6-keto-prostaglandin F1 alpha, adenosine, and tetrahydrocortisol were downregulated (all adjusted false discovery rate [FDR adj] < 0.05). Nine and one dysregulated metabolites were further found in the ROP (t) and ROP (nt) subgroups, respectively. Some of these metabolites exhibited expression levels correlated with postmenstrual age, gestational age, birth weight, and ROP severity in varying degrees. The dysregulated tear metabolites were fundamentally related to vitamin B6, purine, caffeine, arginine, and starch and sucrose metabolism pathways. The 6-keto-prostaglandin F1 alpha obtained the best performance in classifying premature infants with and without ROP (area under the curve [AUC] of 0.893 [range = 0.800-0.986], P < 0.001).

Conclusions: Dysregulated tear metabolites in ROP exhibited abundance correlated with severity of the disease and might be noninvasive biomarkers that potentially serve as complementary screening tools.

早产儿视网膜病变婴儿泪液代谢组学特征的改变。
目的:本研究的目的是研究早产儿视网膜病变(ROP)婴儿泪液的代谢组学特征,并进一步定义无创生物标志物。方法:本前瞻性研究包括47例早产儿94只眼。对23例ROP患儿(需要治疗的15例[ROP (t)],不需要治疗的8例[ROP (nt)])和24例无ROP患儿在表面麻醉后用Schirmer贴收集泪液样本。对瞳孔扩张进行了详细的眼底检查,并记录了人口统计学和出生史数据。采用超高效液相色谱-质谱法进行非靶向泪液代谢组学分析。结果:经性别、经后年龄、胎龄和出生体重调整后,在145种被量化的代谢物中,与非ROP早产儿相比,ROP婴儿泪液中的3,5-二叔丁基-4-羟基苯甲醛、咖啡因和藻糖被鉴定为上调,而尿酸、二homo-γ-亚麻酸、诺卡酮、吡脲醛、鸟氨酸、6-酮-前列腺素F1 α、腺苷、四氢皮质醇下调(所有校正错误发现率[FDR adj] < 0.05)。在ROP (t)和ROP (nt)亚组中分别发现了9种和1种失调代谢物。其中一些代谢物的表达水平与经后年龄、胎龄、出生体重和ROP严重程度有不同程度的相关性。泪液代谢紊乱与维生素B6、嘌呤、咖啡因、精氨酸、淀粉和蔗糖代谢途径有关。6-keto-前列腺素F1 α在早产儿ROP和ROP的分类中表现最好(曲线下面积[AUC]为0.893[范围= 0.800-0.986],P < 0.001)。结论:ROP中失调的泪液代谢物与疾病的严重程度相关,可能是一种无创生物标志物,有可能作为补充筛查工具。
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来源期刊
CiteScore
6.90
自引率
4.50%
发文量
339
审稿时长
1 months
期刊介绍: Investigative Ophthalmology & Visual Science (IOVS), published as ready online, is a peer-reviewed academic journal of the Association for Research in Vision and Ophthalmology (ARVO). IOVS features original research, mostly pertaining to clinical and laboratory ophthalmology and vision research in general.
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