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Urine Nuclear Magnetic Resonance (NMR) Metabolomics in Age-Related Macular Degeneration.
Journal of Proteome Research ( IF 3.8 ) Pub Date : 2019-02-06 , DOI: 10.1021/acs.jproteome.8b00877
Inês Laíns 1, 2, 3, 4 , Daniela Duarte 5 , António S Barros 5 , Ana Sofia Martins 5 , Tatiana J Carneiro 5 , João Q Gil 2, 3, 4 , John B Miller 1 , Marco Marques 2, 3, 4 , Tânia S Mesquita 3 , Patrícia Barreto 3 , Ivana K Kim 1 , Maria da Luz Cachulo 2, 3, 4 , Demetrios G Vavvas 1 , Isabel M Carreira 2 , Joaquim Neto Murta 2, 4 , Rufino Silva 2, 3, 4 , Joan W Miller 1 , Deeba Husain 1 , Ana M Gil 5
Affiliation  

Biofluid biomarkers of age-related macular degeneration (AMD) are still lacking, and their identification is challenging. Metabolomics is well-suited to address this need, and urine is a valuable accessible biofluid. This study aimed to characterize the urinary metabolomic signatures of patients with different stages of AMD and a control group (>50 years). It was a prospective, cross-sectional study, where subjects from two cohorts were included: 305 from Coimbra, Portugal (AMD patients n = 252; controls n = 53) and 194 from Boston, United States (AMD patients n = 147; controls n = 47). For all participants, we obtained color fundus photographs (for AMD staging) and fasting urine samples, which were analyzed using 1H nuclear magnetic resonance (NMR) spectroscopy. Our results revealed that in both cohorts, urinary metabolomic profiles differed mostly between controls and late AMD patients, but important differences were also found between controls and subjects with early AMD. Analysis of the metabolites responsible for these separations revealed that, even though distinct features were observed for each cohort, AMD was in general associated with depletion of excreted citrate and selected amino acids at some stage of the disease, suggesting enhanced energy requirements. In conclusion, NMR metabolomics enabled the identification of urinary signals of AMD and its severity stages, which might represent potential metabolomic biomarkers of the disease.

中文翻译:


年龄相关性黄斑变性的尿液核磁共振 (NMR) 代谢组学。



年龄相关性黄斑变性(AMD)的生物流体生物标志物仍然缺乏,并且其识别具有挑战性。代谢组学非常适合满足这一需求,而尿液是一种有价值的生物流体。本研究旨在表征不同阶段 AMD 患者和对照组(> 50 岁)的尿液代谢组学特征。这是一项前瞻性横断面研究,其中包括来自两个队列的受试者:来自葡萄牙科英布拉的 305 名受试者(AMD 患者 n = 252;对照组 n = 53)和来自美国波士顿的 194 名受试者(AMD 患者 n = 147;对照组) n = 47)。我们为所有参与者提供了彩色眼底照片(用于 AMD 分期)和空腹尿液样本,并使用 1H 核磁共振 (NMR) 光谱进行分析。我们的结果显示,在两个队列中,对照和晚期 AMD 患者之间的尿代谢组谱差异最大,但对照和早期 AMD 受试者之间也发现了重要差异。对负责这些分离的代谢物的分析表明,尽管每个组群都观察到不同的特征,但AMD通常与疾病某些阶段排出的柠檬酸盐和选定氨基酸的消耗有关,这表明能量需求增加。总之,NMR 代谢组学能够识别 AMD 的尿液信号及其严重程度阶段,这可能代表该疾病的潜在代谢组生物标志物。
更新日期:2019-02-07
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