Abstract
Purpose :
Herpes simplex keratitis (HSK), triggered by reactivation of type 1 herpes simplex virus (HSV), is a severe infectious disease leading to vision loss. HSV influences metabolic reprogramming in host cell and alters the cargo of the extracellular vesicles (EV). However, the specific EV metabolic signatures during ocular HSV infection remain unexplored. Our study aims to delineate the EV-associated metabolic profile in tears of HSK patients.
Methods :
We collected 82 samples from 41 participators with unilateral HSK, using contralateral unaffected tears as a control. Our cohort included 13 cases of epithelial HSK, 20 stromal HSK, and 8 of endothelial HSK. Tear EVs were isolated using EXODUS method, and metabolic analysis was conducted via LC-MS/MS. We identified metabolic signatures indicative of HSK and its subtypes using differential analysis and machine learning algorithms.
Results :
Affected eyes exhibited hypopsia and increased extracellular CD63 levels. From tear-derived sEVs, 339 metabolites were identified. Our analysis highlighted changes in energy and amino acid metabolism, alongside alterations in the infectious microenvironment. Notably, we found dysregulated in specific metabolites like methyldopa, linked to abnormal neovascularization and loss of corneal sensation, exacerbating HSK severity, especially in stromal subtypes. Additionally, machine learning classification indicated a potential diagnostic marker panel for pan-keratitis (6-hydroxy-3-succinoylpyridine, 4-nitrocatechol, 2-furoic acid, His-Ser, and tetraethylene-glycol) for pan-keratitis diagnosis.
Conclusions :
Our research reveals that tear EV metabolites are significant indicator for understanding the pathophysiological mechanisms of HSK. These insights could pave the way for the development of liquid biopsy methods and the discovery of new therapeutic targets.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.