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Antti Jylhä, Ulla Aapola, Janika Nättinen, Matti Nykter, Roger W Beuerman, Hannu M T Uusitalo; Tear proteome reveals predictive biomarkers for clinical improvement in glaucoma patients switching from preserved to preservative free medication. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3674.
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Many glaucoma patients experience adverse effects due to long-term use of topical glaucoma medication especially with benzalkonium chloride (BAK) preserved formulations. The purpose of the study was to find predictive biomarkers from the tear proteome data correlating with the improvement of clinical symptoms and signs of the patients after changing the preserved glaucoma medication to preservative-free.
15 glaucoma patients, which had been using BAK-preserved latanoprost for at least two years were chosen for the study. Topical medication of the patients were changed to preservative-free tafluprost and Schirmer strip tear samples were taken at 0, 1.5, 3, 6, 12 months. During each visit clinical symptoms and signs were thoroughly recorded and used later to stratify patients. Protein expression levels in each tear sample were compared between these groups. Relative quantification of tear proteins was done by NanoLC-TripleMSTOF using SWATH. Statistical and MS data analysis were performed with extensive software by AB Sciex.<br /> .
SWATH library for >750 proteins was created and >550 proteins in each sample were relatively quantified. In the baseline samples several proteins showed differential expression levels between two patient groups including e.g. proteins involved in inflammation (PRR4 and AMYC1), cell survival and cell cycle proteins (IGJ, TNFSF13, TP35I3 and STK10). These proteins showed 2-5 times higher expression (p ≤ 0.05) in patients who improved in their clinical score during the study. Immune response related proteins PSMB6, C4B, C9, SERPINB4 and HMGB1 showed significant difference in expression levels between the two groups (≥2 times lower expression in patients who improved their clinical score, p ≤ 0.05).
The results indicate that patients whose clinical scores improve when using preservative-free drug show decreased expression levels of immune response related proteins which also reflects to cell cycle and cell survival proteins higher abundance in same patients tears. These proteins could be used as biomarkers when choosing a suitable treatment for adverse reactions to BAK-preserved glaucoma medication. Potential novel proteomic biomarkers found in this study will be further analyzed in ongoing clinical studies of glaucoma patients.
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