青光眼代谢组学分析提示线粒体功能障碍、衰老和多胺缺乏。

A Metabolomics Profiling of Glaucoma Points to Mitochondrial Dysfunction, Senescence, and Polyamines Deficiency.

机构信息

Equipe Mitolab, Institut Mitovasc, Centre National de la Recherche Scientifique 6015, Institut National de la Santé et de la Recherche Médicale (INSERM) U1083, Université d'Angers, Angers, France.

Département d'Ophtalmologie, Centre Hospitalier Universitaire, Angers, France.

出版信息

Invest Ophthalmol Vis Sci. 2018 Sep 4;59(11):4355-4361. doi: 10.1167/iovs.18-24938.

DOI:10.1167/iovs.18-24938

PMID:30193307

Abstract

PURPOSE

To determine the plasma metabolomic signature of primary open-angle glaucoma (POAG).

METHODS

We compared the metabolomic profiles of plasma from individuals with POAG (n = 36) with age- and sex-matched controls with cataract (n = 27). A targeted metabolomics study was performed using the standardized p180 Biocrates Absolute IDQ p180 kit with a QTRAP 5500 mass spectrometer. Multivariate analyses were performed using principal component analysis (PCA) and the least absolute shrinkage and selection operator (LASSO) method.

RESULTS

Among the 151 metabolites accurately measured, combined univariate and multivariate analyses revealed 18 discriminant metabolites belonging to the carbohydrate, acyl-carnitine, phosphatidylcholine, amino acids, and polyamine families. The metabolomic signature of POAG points to three closely interdependent pathophysiologic conditions; that is, defective mitochondrial oxidation of energetic substrates, altered metabolism resembling that observed in senescence, and a deficiency in spermidine and spermine, both polyamines being involved in the protection of retinal ganglion cells.

CONCLUSIONS

Our results highlight a systemic and age-related mitochondrial defect in the pathogenesis of POAG.

摘要

目的

确定原发性开角型青光眼（POAG）的血浆代谢组学特征。

方法

我们比较了 36 名 POAG 患者（n=36）和 27 名年龄和性别匹配的白内障对照者（n=27）的血浆代谢组学特征。使用标准化的 p180 Biocrates Absolute IDQ p180 试剂盒和 QTRAP 5500 质谱仪进行靶向代谢组学研究。使用主成分分析（PCA）和最小绝对收缩和选择算子（LASSO）方法进行多变量分析。

结果

在准确测量的 151 种代谢物中，联合单变量和多变量分析显示出 18 种具有鉴别意义的代谢物，属于碳水化合物、酰基肉碱、磷脂酰胆碱、氨基酸和多胺家族。POAG 的代谢组学特征指向三种密切相关的病理生理状况，即能量底物的线粒体氧化功能缺陷、类似于衰老时观察到的代谢变化以及亚精胺和精胺缺乏，这两种多胺均参与了保护视网膜神经节细胞。