Metabolomic Disparities in Intraocular Fluid Across Varied Stages of Cataract Progression: Implications for the Analysis of Cataract Development.

IF 1.9 4区 医学 Q2 OPHTHALMOLOGY Journal of Ocular Pharmacology and Therapeutics Pub Date : 2024-10-01 Epub Date: 2024-07-08 DOI:10.1089/jop.2024.0067
Arturs Zemitis, Juris Vanags, Jingzhi Fan, Kristaps Klavins, Guna Laganovska
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Abstract

Introduction: The lens's metabolic demands are met through a continuous circulation of aqueous humor, encompassing a spectrum of components such as organic and inorganic ions, carbohydrates, glutathione, urea, amino acids, proteins, oxygen, carbon dioxide, and water. Metabolomics is a pivotal tool, offering an initial insight into the complexities of integrated metabolism. In this investigative study, we systematically scrutinize the composition of intraocular fluid in individuals afflicted with cataracts. Methods: The investigation involved a comprehensive analysis of aqueous humor samples from a cohort comprising 192 patients. These individuals were stratified by utilizing the SPONCS classification system, delineating distinct groups characterized by the hardness of cataracts. The analytical approach employed targeted quantitative metabolite analysis using HILIC-based liquid chromatography coupled with high-resolution mass spectrometric detection. The metabolomics data analysis was performed with MetaboAnalyst 5.0. Results: The results of the enrichment analysis have facilitated the inference that the discerned disparities among groups arise from disruptions in taurine and hypotaurine metabolism, variations in tryptophan metabolism, and modifications in mitochondrial beta-oxidation of short-chain saturated fatty acids and pyrimidine metabolism. Conclusion: A decline in taurine concentration precipitates diminished glutathione activity, prompting an elevated requirement for NAD+ and instigating tryptophan metabolism along the kynurenine pathway. Activation of this pathway is additionally prompted by interferon-gamma and UV radiation, leading to the induction of IDO. Concurrently, heightened mitochondrial beta-oxidation signifies a distinctive scenario in translocating fatty acids into the mitochondria, enhancing energy production.

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白内障不同发展阶段的眼内液代谢组差异:白内障发展分析的意义。
导言:晶状体的新陈代谢需求是通过持续循环的房水来满足的,房水中包含多种成分,如有机和无机离子、碳水化合物、谷胱甘肽、尿素、氨基酸、蛋白质、氧气、二氧化碳和水。代谢组学是一种重要的工具,可帮助我们初步了解综合代谢的复杂性。在这项调查研究中,我们系统地检查了白内障患者眼内液的成分。调查方法调查包括对 192 名白内障患者的眼内液样本进行全面分析。利用 SPONCS 分类系统对这些患者进行了分层,根据白内障的硬度划分出不同的群体。分析方法采用基于 HILIC 的液相色谱法和高分辨率质谱检测技术,对代谢物进行有针对性的定量分析。代谢组学数据分析采用 MetaboAnalyst 5.0 进行。结果富集分析的结果有助于推断各组之间的差异是由于牛磺酸和低牛磺酸代谢紊乱、色氨酸代谢变化以及线粒体中短链饱和脂肪酸β-氧化和嘧啶代谢的改变造成的。结论牛磺酸浓度下降会导致谷胱甘肽活性减弱,从而增加对 NAD+ 的需求,并通过犬尿氨酸途径促进色氨酸代谢。干扰素-γ 和紫外线辐射也会激活这一途径,从而诱导 IDO。与此同时,线粒体β-氧化作用的增强标志着将脂肪酸转运到线粒体的独特情景,从而提高了能量的产生。
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来源期刊
CiteScore
4.60
自引率
4.30%
发文量
72
审稿时长
1 months
期刊介绍: Journal of Ocular Pharmacology and Therapeutics is the only peer-reviewed journal that combines the fields of ophthalmology and pharmacology to enable optimal treatment and prevention of ocular diseases and disorders. The Journal delivers the latest discoveries in the pharmacokinetics and pharmacodynamics of therapeutics for the treatment of ophthalmic disorders. Journal of Ocular Pharmacology and Therapeutics coverage includes: Glaucoma Cataracts Retinal degeneration Ocular infection, trauma, and toxicology Ocular drug delivery and biotransformation Ocular pharmacotherapy/clinical trials Ocular inflammatory and immune disorders Gene and cell-based therapies Ocular metabolic disorders Ocular ischemia and blood flow Proliferative disorders of the eye Eyes on Drug Discovery - written by Gary D. Novack, PhD, featuring the latest updates on drug and device pipeline developments as well as policy/regulatory changes by the FDA.
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