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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<jats:italic>vs<\/jats:italic>. CTRL, DRYaq<jats:italic>vs<\/jats:italic>. CTRL and DRYaqlip<jats:italic>vs<\/jats:italic>. 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.<\/jats:p>","DOI":"10.1038\/srep29629","type":"journal-article","created":{"date-parts":[[2016,7,20]],"date-time":"2016-07-20T08:50:47Z","timestamp":1469004647000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":119,"title":["Proteomics analysis of human tears from aqueous-deficient and evaporative dry eye patients"],"prefix":"10.1038","volume":"6","author":[{"given":"Natarajan","family":"Perumal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Funke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Pfeiffer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franz H.","family":"Grus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,7,20]]},"reference":[{"key":"BFsrep29629_CR1","doi-asserted-by":"crossref","unstructured":"DEWS. 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