Tear metabolomics reveals novel potential biomarkers in epithelial herpes simplex keratitis

Abstract Background Herpes simplex keratitis (HSK) is a recurrent inflammatory disease of cornea primarily initiated by type I herpes simplex virus infection of corneal epithelium. However, early diagnosis of HSK remains challenging due to the lack of specific biomarkers. This study aims to identify...

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Main Authors: Jinyu Zhang, Zhenning Wu, Yangqi Zhang, Kaili Wu, Xiaoyi Li, Shiyou Zhou
Format: Article
Language:English
Published: BMC 2025-01-01
Series:BMC Ophthalmology
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Online Access:https://doi.org/10.1186/s12886-025-03875-6
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author Jinyu Zhang
Zhenning Wu
Yangqi Zhang
Kaili Wu
Xiaoyi Li
Shiyou Zhou
author_facet Jinyu Zhang
Zhenning Wu
Yangqi Zhang
Kaili Wu
Xiaoyi Li
Shiyou Zhou
author_sort Jinyu Zhang
collection DOAJ
description Abstract Background Herpes simplex keratitis (HSK) is a recurrent inflammatory disease of cornea primarily initiated by type I herpes simplex virus infection of corneal epithelium. However, early diagnosis of HSK remains challenging due to the lack of specific biomarkers. This study aims to identify biomarkers for HSK through tear metabolomics analysis between HSK and healthy individuals. Methods We conducted a cross-sectional study enrolling 33 participants. Tear samples were collected from one eye of 18 HSK patients and 15 healthy volunteers using Schirmer-strips. Tear metabolomic profiling was performed using high-performance liquid chromatography tandem mass spectrometry (LC–MS/MS). Metabolites were quantified and matched against entries in the human metabolome database (HMDB) and small molecule pathway database (SMPDB) to identify metabolites and metabolic pathways, respectively. Metabolic differences between HSK and control group were determined using multivariate statistical analysis. Results A total of 329 metabolites were identified, of which 18 were significantly altered in HSK patients. Notably, 12 metabolites were significantly increased, and 6 were significantly decreased in HSK patients. The changed metabolites were enriched in these pathways: arginine and proline metabolism, phospholipid biosynthesis, alpha linolenic acid and linoleic acid metabolism, retinol metabolism. To assess the potential utility of tear biomarkers, a predictive model was developed combining 4 metabolites (AUC = 0.998 [95%CI: 0.975, 1]): D-proline, linoelaidic acid, plantagonine, and phosphorylcholine. Conclusions Our study establishes that HSK has a distinctive metabolomic profile, with 4 key elements maybe emerging as potential biomarkers for diagnostic purposes. These findings may provide novel insights into early and rapid diagnosis of HSK.
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issn 1471-2415
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spelling doaj-art-609f145692b3460db142578977c5c83b2025-01-26T12:21:02ZengBMCBMC Ophthalmology1471-24152025-01-012511910.1186/s12886-025-03875-6Tear metabolomics reveals novel potential biomarkers in epithelial herpes simplex keratitisJinyu Zhang0Zhenning Wu1Yangqi Zhang2Kaili Wu3Xiaoyi Li4Shiyou Zhou5State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular DiseasesState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular DiseasesState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular DiseasesState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular DiseasesZhaoke (Guangzhou) Ophthalmology Pharmaceutical LimitedState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular DiseasesAbstract Background Herpes simplex keratitis (HSK) is a recurrent inflammatory disease of cornea primarily initiated by type I herpes simplex virus infection of corneal epithelium. However, early diagnosis of HSK remains challenging due to the lack of specific biomarkers. This study aims to identify biomarkers for HSK through tear metabolomics analysis between HSK and healthy individuals. Methods We conducted a cross-sectional study enrolling 33 participants. Tear samples were collected from one eye of 18 HSK patients and 15 healthy volunteers using Schirmer-strips. Tear metabolomic profiling was performed using high-performance liquid chromatography tandem mass spectrometry (LC–MS/MS). Metabolites were quantified and matched against entries in the human metabolome database (HMDB) and small molecule pathway database (SMPDB) to identify metabolites and metabolic pathways, respectively. Metabolic differences between HSK and control group were determined using multivariate statistical analysis. Results A total of 329 metabolites were identified, of which 18 were significantly altered in HSK patients. Notably, 12 metabolites were significantly increased, and 6 were significantly decreased in HSK patients. The changed metabolites were enriched in these pathways: arginine and proline metabolism, phospholipid biosynthesis, alpha linolenic acid and linoleic acid metabolism, retinol metabolism. To assess the potential utility of tear biomarkers, a predictive model was developed combining 4 metabolites (AUC = 0.998 [95%CI: 0.975, 1]): D-proline, linoelaidic acid, plantagonine, and phosphorylcholine. Conclusions Our study establishes that HSK has a distinctive metabolomic profile, with 4 key elements maybe emerging as potential biomarkers for diagnostic purposes. These findings may provide novel insights into early and rapid diagnosis of HSK.https://doi.org/10.1186/s12886-025-03875-6Herpes simplex keratitisTear metabolitesMetabolomics
spellingShingle Jinyu Zhang
Zhenning Wu
Yangqi Zhang
Kaili Wu
Xiaoyi Li
Shiyou Zhou
Tear metabolomics reveals novel potential biomarkers in epithelial herpes simplex keratitis
BMC Ophthalmology
Herpes simplex keratitis
Tear metabolites
Metabolomics
title Tear metabolomics reveals novel potential biomarkers in epithelial herpes simplex keratitis
title_full Tear metabolomics reveals novel potential biomarkers in epithelial herpes simplex keratitis
title_fullStr Tear metabolomics reveals novel potential biomarkers in epithelial herpes simplex keratitis
title_full_unstemmed Tear metabolomics reveals novel potential biomarkers in epithelial herpes simplex keratitis
title_short Tear metabolomics reveals novel potential biomarkers in epithelial herpes simplex keratitis
title_sort tear metabolomics reveals novel potential biomarkers in epithelial herpes simplex keratitis
topic Herpes simplex keratitis
Tear metabolites
Metabolomics
url https://doi.org/10.1186/s12886-025-03875-6
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