Abstract
To understand the pathophysiology of dry eye disease (DED), it is necessary to characterize proteins in the ocular surface fluids, including tear fluid (TF) and lacrimal fluid (LF). There have been several reports of TF proteomes, but few proteomic studies have examined LF secreted from the lacrimal gland (LG). Therefore, we characterized the proteins constituting TF and LF by liquid chromatography mass spectrometry. TF and LF were collected from patients with non-Sjögren syndrome DED and from healthy subjects. Through protein profiling and label-free quantification, 1165 proteins from TF and 1448 from LF were identified. In total, 849 proteins were present in both TF and LF. Next, candidate biomarkers were verified using the multiple reaction monitoring assay in both TF and LF of 17 DED patients and 17 healthy controls. As a result, 16 marker proteins were identified (fold-change > 1.5, p-value < 0.05), of which 3 were upregulated in TF and 8 up- and 5 down-regulated in LF. In conclusion, this study revealed novel DED markers originating from the LG and tears by in-depth proteomic analysis and comparison of TF and LF proteins.
Highlights
Analysis of human body fluids is important for identifying the cause of disease and biomarkers for diagnosing the disease[1,2]
We isolated and identified nearly 1700 proteins from ocular surface fluid, while only several hundred proteins have been previously documented in proteomics analyses of human TF16–19
This study represents the largest number of ocular surface fluid proteins of dry eye disease (DED) patients identified to date
Summary
Analysis of human body fluids is important for identifying the cause of disease and biomarkers for diagnosing the disease[1,2]. Among the sources for liquid biopsy, tear fluid (TF) representing ocular fluid is not frequently used, but is a good source for non-invasive investigation, as it is easy to assess and clear and it exhibits limited bacterial contamination. Identifying reliable biomarkers for diagnosis, assessment of disease severity, and evaluation of prognosis is essential for understanding the pathophysiology of the disease and treating DED patients. Several studies have outlined the proteomic analysis of TF from patients with DED16–19. We investigated disease-specific biomarkers in prospective manner by comparing individual proteomes in TF and LF between normal and DED groups
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