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. 2016 Jul 20:6:29629.
doi: 10.1038/srep29629.

Proteomics analysis of human tears from aqueous-deficient and evaporative dry eye patients

Natarajan Perumal  1 , Sebastian Funke  1 , Norbert Pfeiffer  1 , Franz H Grus  1
Affiliations

Proteomics analysis of human tears from aqueous-deficient and evaporative dry eye patients

Natarajan Perumal et al. Sci Rep. .

Abstract

Despite the high global prevalence of dry eye syndrome (DES), the fundamental processes underlying this pathology remain largely unexplored. Therefore, this study endeavoured to investigate in-depth the tear proteome of DES patients employing the mass spectrometry (MS)-based proteomic strategies. Eighty patients were recruited and subdivided into three major DES subgroups, which are the aqueous-deficient (DRYaq), evaporative (DRYlip) and a combination of the two (DRYaqlip), as well as healthy subjects (CTRL). Discovery proteomics strategy was employed to identify large number of significantly differentially expressed tear proteins in DRYlip vs. CTRL, DRYaq vs. CTRL and DRYaqlip vs. CTRL with 22, 58 and 67 proteins, respectively. Biological functional analysis demonstrated for the first time that various metabolic processes were highly expressed in DRYaq and DRYaqlip, which might modulate various other known processes, especially the inflammatory and immune processes. Targeted proteomics strategy verified that 13 major proteins were differentially expressed in specific DES subgroups, comprising of PRR4, ZG16B, SCGB2A1, DMBT1, PROL1, LACRT, ALDH3A1, ENO1, TF, S100A8, S100A9, PEBP1 and ORM1. In conclusion, this study had explored in-depth the pathology of DES by unravelling various new fundamental processes and the major proteins responsible for the maintenance of tear film stability.

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Figures

Figure 1
Figure 1. Discovery proteomics analysis via1DE & LC-ESI-MS/MS strategy reveals the characteristics of the tear proteome of DES patients.
(a) Representative tear protein profiles of the DES subgroups and CTRL resolved in 1DE gel after colloidal blue staining. (b) The degree of variances in the proteome between the DES subgroups and CTRL investigated by Pearson correlation analysis. (c) The heat map shows hierarchical clustering analysis of the 200 tear proteins that separates the designated groups into two main clusters. (d) The bar chart shows the degree of protein abundance in DES subgroups and CTRL.
Figure 2
Figure 2
The bar charts shows the over-represented GOBP terms associated with the differentially expressed proteins analysed employing the DAVID tool in (a) DRYlip vs. CTRL, (b) DRYaq vs. CTRL and (c) DRYaqlip vs. CTRL.
Figure 3
Figure 3
The bar charts shows the over-represented GOCC terms associated with the differentially expressed proteins analysed employing the Ingenuity Pathways Analysis software in (a) DRYlip vs. CTRL, (b) DRYaq vs. CTRL and (c) DRYaqlip vs. CTRL.
Figure 4
Figure 4
The bar charts shows the over-represented molecular type terms associated with the differentially expressed proteins analysed employing the Ingenuity Pathways Analysis software in (a) DRYlip vs. CTRL, (b) DRYaq vs. CTRL and (c) DRYaqlip vs. CTRL.
Figure 5
Figure 5
Networks of PPI of the significantly differentially expressed tear proteins analysed employing the Ingenuity Pathways Analysis software in (a) DRYlip vs. CTRL, (b) DRYaq vs. CTRL and (c) DRYaqlip vs. CTRL.
See this image and copyright information in PMC

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