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Sebastian Funke, Katrin Lorenz, Marion Kotterer, Sabine Beck, Wolters Dominik, Norbert Pfeiffer, Franz H Grus, Experimental Ophthalmology, University Medical Center, Mainz, Germany; Analysis of the Effects of Taflotan® Sine on Tear Protein Profiles. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1474.
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© ARVO (1962-2015); The Authors (2016-present)
By use of proteomic methods tear film changes due to a therapeutic switch from common IOP lowering medication Xalatan® (latanoprost) to preservative-free Taflotan® sine in POAG patients should be studied for the assessment of the ocular surface health status.
The research project was approved by the local ethics committee (No. 837.453.10 ). Schirmer tears of POAG patients (N=19) switching from Xalatan® to Taflotan® sine were analyzed by use of a gel-based LC ESI Orbitrap XL mass spectrometric workflow to reveal protein candidates responding to Taflotan® sine application in a representative sample pool (N=3/ 0, 2, 12, 24 weeks). Longitudinal analysis of tear proteins was realized considering linear and non-linear analysis methods. Revealed candidate proteins as well as established dry eye markers and cytokines were selected for antibody based microarray validation assays comparing protein levels between POAG patients and healthy controls. Finally, candidate proteins were examined for localization and corresponding biological functions.
By use of the LC ESI workflow more than 1000 proteins in POAG patient tears could be identified. Regression analysis (p<0.05, R2≥0.9) demonstrated response in 12% of tear proteins after the medical switch. Predominantly level declines in the course of Taflotan® sine appliance could be revealed. Additional fold change cluster analysis illuminated response of further proteins. Predominantly intracellular originated tear proteins were affected showing a level decrease in most of the cases. Microarray validation supported the regulation of most of the candidate proteins. Thereby annexin 11, cadherin 5, plectin, serotransferrin, kinectin and pyruvate kinase isozymes M1/M2 manifested a distinct approximation to the healthy level. Also dry eye markers like mammaglobin B and cytokines shifted towards the healthy level in the course of Taflotan® sine utilization. Accordingly a regeneration of the ocular surface indicated by a decline in epithelial leakage proteins, cytokines and dry eye associated proteins could be proposed.
A distinct change in the tear proteomic pattern after a therapeutic switch from Xalatan® to preservative-free Taflotan® sine in POAG patients could be demonstrated, whereby the portion of leakage proteins and inflammatory cytokines was shown to be receded in the course of the study reflecting an improvement of ocular surface conditions.
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