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Natarajan Perumal, Caroline Manicam, Alexandra Tschäbunin, Maya Scieranski, Aline Ratcliffe, Laura Gronbach, Norbert Pfeiffer, Franz H Grus; Discriminant Proteomic Analysis of Dry Eye Syndrome and Glaucoma: Deciphering the Protein Code Underlying the Double Trouble. Invest. Ophthalmol. Vis. Sci. 2019;60(9):263.
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© ARVO (1962-2015); The Authors (2016-present)
Dry eye (DES) and glaucoma (GLM) are two most common yet debilitating ocular disorders, which also co-occur owing to the use of GLM medication. To date, the molecular mechanisms and alterations in the regulation of protein mediators in different DES subgroups are still obscure, and inter-individual variations in disease diagnosis remain elusive. Hence, this study characterized the changes in human tear proteome to distinguish different subtypes of DES and to unravel the underlying molecular processes in a personalized basis.
Tear samples were collected with Schirmer strips from 180 individuals following stringent clinical classifications and categorized as aqueous-deficient DES (DRYaq: n=30), evaporative DES (DRYlip: n=30) and a combination of DES (DRYaqlip: n=30), glaucoma (GLM; n=20), a combination of DRYaqlip and glaucoma (GLM_DRY; n=20) and healthy subjects (CTRL; n=50). Samples were analyzed individually utilizing a targeted mass spectrometry (MS)-based proteomics strategy. The acquired continuum MS spectra were analyzed by MaxQuant computational platform followed by functional annotation and pathway analyses.
A total of 128 signature peptides representing key tear protein isoforms were utilized for the targeted MS analysis. Among these, 13, 32, 33, 14 and 28 proteins were significantly (p<0.05) differentially expressed in the DRYlip, DRYaq, DRYaqlip, GLCM and GLCM_DES groups compared to CTRL, respectively. Noteworthy is that several protein clusters involved in metabolic, inflammatory and immune processes were highly activated in DRYaq, and proteins involved in lipid metabolism were significantly regulated in DRYlip. Interestingly, proteins related to heightened neurological processes were specifically regulated in both GLCM and GLCM_DES. These potential markers were also highly correlated to severity of the disease, and to age and gender. Notably, there are inter-individual variations in the expressions of specific isoforms such as S100A9, ALDH3A1, PRR4 and IGHA1.
This is the first study demonstrating the significant discriminant proteomic analysis of DES subtypes including GLM in a personalized manner in a large cohort. Targeted proteomics strategy was instrumental to unravel novel molecular processes in different DES for development of specific diagnosis and prognosis for both pathologies.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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