Abstract
BackgroundHerpes simplex virus type 1 (HSV-1) keratitis is a major cause of corneal blindness in the world, and an in-depth understanding of its pathogenesis may help improve existing diagnosis and treatment. The purpose of this study is to compare and analysis the total tear protein profile of HSV-1 epithelial keratitis patients, and to quantify the potential candidate biomarkers of HSV-1 epithelial keratitis.MethodsWe investigated the proteome in tear fluid from three HSV-1 epithelial keratitis patients and three healthy control subjects using nano-scale liquid chromatography-tandem mass spectrometry (nLC-MS/MS) analysis. Functional annotation of differentially expressed proteins was done with the Gene Ontology (GO) analysis. ELISA was done to quantify the potential candidate biomarkers in 26 clinical cases.ResultsTear fluid from three HSV-1 epithelial keratitis patients and three healthy control subjects contained a total of 1275 proteins and 326 proteins were unique to tear fluid of HSV-1 epithelial keratitis patients. Bioinformatics analysis revealed that tear proteins from HSV-1 epithelial keratitis patients may be involved in metabolic processes, antigen presentation, inflammatory response, and in the TNF-mediated and T cell receptor pathways. Furthermore, IL1A, IL12B, DEFB4A, and CAMP, which are associated with the inflammatory response and inhibition of viral infection, were significantly more abundant in the HSV-1 epithelial keratitis patients than in the healthy control subjects.ConclusionsThis study reports the proteomic profile of tears in HSV-1 epithelial keratitis for the first time and identifies a number of unique differentially expressed proteins.
Highlights
Herpes simplex virus type 1 (HSV-1) keratitis is a major cause of corneal blindness in the world, and an in-depth understanding of its pathogenesis may help improve existing diagnosis and treatment
Highly abundant proteins such as lactotransferrin, lipocalin 1, lipocalin 2, albumin, lysozyme, Fig. 1 Schematic diagram of proteomics experiments and Venn diagrams of the identified proteins. a Schematic overview of the proteomic analysis of tear fluid. b Tear proteins unique to and shared between 3 HSV-1 epithelial keratitis patients and 3 healthy control subjects. c Unique and shared tear proteins of HSV-1 epithelial keratitis patients and healthy control subjects complement C3, and immunoglobulin heavy constant alpha 1 were present in tears of individuals from both groups
By comparing our tear proteome data with their tear proteome data reference set, we found that 1026 proteins (80.5% of total 1275 proteins) were common, while 952 proteins were identified in healthy control subjects, and 596 proteins were identified in HSV-1 epithelial keratitis patients
Summary
Herpes simplex virus type 1 (HSV-1) keratitis is a major cause of corneal blindness in the world, and an in-depth understanding of its pathogenesis may help improve existing diagnosis and treatment. Tears are a complex biological mixture known to have electrolytes, lipids, enzymes, metabolites, small organic molecules, and proteins [8]. Their main function is to provide lubrication and nutrition to the cornea, and become the first line of defense against pathogens [8]. Studying the characterization of proteomic changes associated with HSV-1 epithelial keratitis will help to elucidate its pathogenesis, and further identify the therapeutic targets of disease
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