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年龄相关的人眼玻璃体液代谢组学改变在细菌性眼内炎中的研究

Age-Associated Alterations in the Metabolome of Human Vitreous in Bacterial Endophthalmitis.

机构信息

Jhaveri Microbiology Centre, Brien Holden Eye Research Centre, LV Prasad Eye Institute, Hyderabad, India.

Center for Doctoral Studies, Manipal Academy of Higher Education, Karnataka, India.

出版信息

Invest Ophthalmol Vis Sci. 2024 Nov 4;65(13):6. doi: 10.1167/iovs.65.13.6.

DOI:10.1167/iovs.65.13.6
PMID:39499509
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11540026/
Abstract

PURPOSE

Endophthalmitis is a severe inflammatory condition due to intraocular infections that often leads to irreversible blindness. This study aimed to understand the age-dependent metabolic alterations in the vitreous of patients with bacterial endophthalmitis.

METHODS

The study included the vitreous metabolome of patients with bacterial endophthalmitis (group 1, n = 15) and uninfected controls (group 2, n = 14), which were further stratified into three groups according to their age: young (0-30 years), middle (31-60 years), and elderly (>60 years). Vitreous samples were subjected to untargeted metabolomic analysis using high-resolution mass spectrometry (HRMS)m and acquired mass spectrometry data were analyzed using MetaboAnalyst 6.0. The altered metabolites with log2FC of ≥2/≤2, P < 0.05, and variable importance in projection > 1 were considered significant.

RESULTS

In a total of 109 endogenous metabolites identified, young and elderly patients with endophthalmitis showed 52 (elevated, 25; reduced, 27; P < 0.05) and 27 (elevated, 19; reduced, 8; P < 0.05) significantly altered metabolites, respectively, compared to their age-matched controls. Additionally, 27 metabolites were differentially expressed in young patients with endophthalmitis compared to the older group. The crucial metabolic pathways dysregulated in the older infected population were de novo purine synthesis and salvage, carnitine, polyamine (spermidine), lipids (prostaglandins), and amino acid (taurine, methionine, histidine) which could possibly be attributed to the increased disease severity and inflammation observed in a clinical setting.

CONCLUSIONS

Despite the erratic metabolic changes observed in the younger group infected with endophthalmitis when compared to age-matched controls, dysregulation in the specific pathways such as purine, carnitine, arachidonic acid, and polyamine metabolism could possibly alter the immunological exacerbation observed in the older group.

摘要

目的

眼内炎是一种由眼内感染引起的严重炎症性疾病,常导致不可逆转的失明。本研究旨在了解细菌性眼内炎患者玻璃体中与年龄相关的代谢变化。

方法

本研究纳入了细菌性眼内炎患者(第 1 组,n=15)和未感染对照者(第 2 组,n=14)的玻璃体代谢组学,根据年龄进一步分为三组:年轻组(0-30 岁)、中年组(31-60 岁)和老年组(>60 岁)。采用高分辨率质谱(HRMS)对玻璃体样本进行非靶向代谢组学分析,并使用 MetaboAnalyst 6.0 分析获得的质谱数据。具有 log2FC≥2/≤2、P<0.05 和投影变量重要性(VIP)>1 的改变代谢物被认为具有统计学意义。

结果

在鉴定出的 109 种内源性代谢物中,与年龄匹配的对照组相比,年轻和老年眼内炎患者分别显示出 52 种(升高,25 种;降低,27 种;P<0.05)和 27 种(升高,19 种;降低,8 种;P<0.05)明显改变的代谢物。此外,与老年组相比,年轻眼内炎患者有 27 种代谢物表达差异。在感染人群中,失调的关键代谢途径包括从头嘌呤合成和补救、肉碱、多胺(精胺)、脂质(前列腺素)和氨基酸(牛磺酸、蛋氨酸、组氨酸),这可能归因于在临床观察到的疾病严重程度和炎症的增加。

结论

尽管与年龄匹配的对照组相比,年轻感染组观察到的代谢变化较为紊乱,但嘌呤、肉碱、花生四烯酸和多胺代谢等特定途径的失调可能改变老年组观察到的免疫加剧。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31c6/11540026/5232766e75d4/iovs-65-13-6-f006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31c6/11540026/61aa780d8d42/iovs-65-13-6-f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31c6/11540026/17ca0d085507/iovs-65-13-6-f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31c6/11540026/f6296a94f491/iovs-65-13-6-f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31c6/11540026/22f0af61e589/iovs-65-13-6-f004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31c6/11540026/4416ef45075c/iovs-65-13-6-f005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31c6/11540026/5232766e75d4/iovs-65-13-6-f006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31c6/11540026/61aa780d8d42/iovs-65-13-6-f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31c6/11540026/17ca0d085507/iovs-65-13-6-f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31c6/11540026/f6296a94f491/iovs-65-13-6-f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31c6/11540026/22f0af61e589/iovs-65-13-6-f004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31c6/11540026/4416ef45075c/iovs-65-13-6-f005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31c6/11540026/5232766e75d4/iovs-65-13-6-f006.jpg

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