National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China; National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China.
National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China; The Key Laboratory for Biomedical Photonics of MOE at Wuhan National Laboratory for Optoelectronics-Hubei Bioinformatics & Molecular Imaging Key Laboratory, Systems Biology Theme, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China.
Ocul Surf. 2024 Jan;31:21-30. doi: 10.1016/j.jtos.2023.12.005. Epub 2023 Dec 19.
Herpes simplex keratitis (HSK), caused by type 1 herpes simplex virus (HSV) reactivation, is a severe infectious disease that leads to vision loss. HSV can trigger metabolic reprogramming in the host cell and change the extracellular vesicles (EV) cargos; however, little is known about the EV metabolic signatures during ocular HSV infection. Here, we aimed to depict the EV-associated metabolic landscape in HSK patients' tears.
We collected 82 samples from 41 participants with unilateral HSK (contralateral unaffected tears were set as negative control), including subtype cohorts of 13 epithelial, 20 stromal, and 8 endothelial HSK. We isolated tear EVs via our previously established platform and conducted metabolic analysis using LC-MS/MS. The metabolic signatures for recognizing HSK and subtypes were assessed through differential analysis and machine learning algorithms.
Hypopsia and increased extracellular CD63 levels were observed in affected eyes. We identified 339 metabolites based on sEVs isolated from tears. Differential analysis revealed alterations in energy and amino acid metabolism, as well as the infectious microenvironment. Furthermore, we observed dysregulated metabolite such as methyldopa, which is associated with inappropriate neovascularization and corneal sensation loss, contributing to the HSK severity particularly in the stromal subtype. Moreover, machine learning classification also suggested a set of EV metabolic signatures that have potential for pan-keratitis detection.
Our findings demonstrate that tear EV metabolites can serve as valuable indicators for comprehending the underlying pathological mechanisms. This knowledge is expected to facilitate the development of liquid biopsy means and therapeutic target discovery.
单纯疱疹病毒性角膜炎（HSK）由 1 型单纯疱疹病毒（HSV）再激活引起，是一种严重的传染病，可导致视力丧失。HSV 可触发宿主细胞的代谢重编程并改变细胞外囊泡（EV）的 cargos；然而，关于眼部 HSV 感染期间 EV 的代谢特征知之甚少。在这里，我们旨在描绘 HSK 患者泪液中 EV 相关的代谢特征。
我们收集了 41 名单侧 HSK 患者（对侧未受影响的眼泪作为阴性对照）的 82 个样本，包括 13 个上皮型、20 个基质型和 8 个内皮型 HSK 亚型队列。我们通过我们之前建立的平台分离泪液 EV，并使用 LC-MS/MS 进行代谢分析。通过差异分析和机器学习算法评估识别 HSK 和亚型的代谢特征。
受影响的眼睛出现视力下降和细胞外 CD63 水平升高。我们基于从眼泪中分离的 sEV 鉴定出 339 种代谢物。差异分析显示能量和氨基酸代谢以及感染微环境发生改变。此外，我们观察到代谢物失调，如甲基多巴，它与不适当的血管生成和角膜感觉丧失有关，特别是在基质型中，对 HSK 严重程度有影响。此外，机器学习分类也表明了一组 EV 代谢特征，它们具有用于全角膜炎检测的潜力。
我们的研究结果表明，泪液 EV 代谢物可以作为理解潜在病理机制的有价值指标。这一知识有望促进液体活检手段和治疗靶点的发现。
