Dmuchowska Diana Anna, Pietrowska Karolina, Krasnicki Pawel, Kowalczyk Tomasz, Misiura Magdalena, Grochowski Emil Tomasz, Mariak Zofia, Kretowski Adam, Ciborowski Michal
Department of Ophthalmology, Medical University of Bialystok, Bialystok, Poland.
Metabolomics Laboratory, Clinical Research Center, Medical University of Bialystok, Bialystok, Poland.
Front Mol Biosci. 2021 May 14;8:682600. doi: 10.3389/fmolb.2021.682600. eCollection 2021.
Pseudoexfoliation syndrome (XFS) is stress- or inflammation-induced elastosis accompanied by excessive production of microfibrils and their deposition in the anterior segment of the eye. Approximately 60-70 million people are affected by XFS worldwide. It is a component of a systemic disorder, considered a major risk factor for accelerated cataract formation, cataract surgery complications and development of glaucoma, which untreated or inadequately treated may lead to blindness. Moreover, XFS has been associated with cardiovascular and cerebrovascular morbidity, dementia, sensorineural hearing loss and pelvic organ prolapse. The pathogenesis of XFS has not been fully elucidated yet. Aqueous humor (AH) is a transparent fluid filling the anterior and posterior chambers of the eye. Determination of AH metabolites that are characteristic for XFS may provide valuable information about the molecular background of this ocular disorder. The aim of this study was to compare the composition of AH in XFS and non-XFS patients undergoing cataract surgery. The AH samples from 34 patients (15 with XFS and 19 without) were analyzed using liquid chromatography coupled to a Quadrupole Time-of-Flight mass spectrometer (LC-QTOF-MS). The obtained metabolic fingerprints were analyzed using multivariate statistics. Eleven statistically significant metabolites were identified. Compared with the non-XFS group, the AH of patients with XFS contained significantly lower levels of amino acids and their derivatives, for example, arginine (-31%, VIP = 2.38) and homo-arginine (-19%, VIP = 1.38). Also, a decrease in the levels of two acylcarnitines, hydroxybutyrylcarnitine (-29%, VIP = 1.24) and decatrienoylcarnitine (-46%, VIP = 1.89), was observed. However, the level of indoleacetaldehyde in XFS patients was significantly higher (+96%, VIP = 2.64). Other significant metabolites were two well-recognized antioxidants, ascorbic acid (-33%, VIP = 2.11) and hydroxyanthranilic acid (-33%, VIP = 2.25), as well as S-adenosylmethionine, a compound with anti-inflammatory properties (-29%, VIP = 1.93). Metabolic pathway analysis demonstrated that the identified metabolites belonged to eight metabolic pathways, with cysteine and methionine metabolism as well as arginine and proline metabolism being the most frequently represented. XFS can be associated with enhanced oxidative stress and inflammation, as well as with the disturbances of cellular respiration and mitochondrial energy production. Implementation of non-targeted metabolomics provided a better insight into the still not fully understood pathogenesis of XFS.
假性剥脱综合征（XFS）是一种由压力或炎症诱导的弹性组织变性，伴有微原纤维过度产生并沉积于眼前节。全球约有6000万至7000万人受XFS影响。它是一种全身性疾病的组成部分，被认为是加速白内障形成、白内障手术并发症及青光眼发生的主要危险因素，未经治疗或治疗不当可能导致失明。此外，XFS还与心血管和脑血管疾病、痴呆、感音神经性听力损失及盆腔器官脱垂有关。XFS的发病机制尚未完全阐明。房水（AH）是填充眼房的透明液体。测定具有XFS特征的房水代谢物可能为这种眼部疾病的分子背景提供有价值的信息。本研究的目的是比较接受白内障手术的XFS患者和非XFS患者房水的成分。使用液相色谱与四极杆飞行时间质谱仪（LC-QTOF-MS）对34例患者（15例XFS患者和19例非XFS患者）的房水样本进行分析。使用多元统计分析获得的代谢指纹图谱。鉴定出11种具有统计学意义的代谢物。与非XFS组相比，XFS患者房水中氨基酸及其衍生物水平显著降低，例如精氨酸（-31%，VIP=2.38）和高精氨酸（-19%，VIP=1.38）。此外，还观察到两种酰基肉碱水平降低，即羟丁酰肉碱（-29%，VIP=1.24）和癸三烯酰肉碱（-46%，VIP=1.89）。然而，XFS患者吲哚乙醛水平显著升高（+96%，VIP=2.64）。其他显著的代谢物是两种公认的抗氧化剂，即抗坏血酸（-33%，VIP=2.11）和羟基邻氨基苯甲酸（-33%，VIP=2.25），以及具有抗炎特性的化合物S-腺苷甲硫氨酸（-29%，VIP=1.93）。代谢途径分析表明，鉴定出的代谢物属于8条代谢途径，其中半胱氨酸和甲硫氨酸代谢以及精氨酸和脯氨酸代谢最为常见。XFS可能与氧化应激和炎症增强以及细胞呼吸和线粒体能量产生紊乱有关。非靶向代谢组学的应用为仍未完全了解的XFS发病机制提供了更好的见解。
