Abstract
Purpose :
Glaucoma patients commonly experience adverse events due to long-term use of benzalkonium chloride (BAK) preserved glaucoma medication. It was hypothesized that the tear proteome would reflect the mechanisms involved in ocular surface adverse reactions such as inflammation. In order to study this concept, the tear proteome was analyzed in patients before and over one year period after switching from a preserved to an unpreserved prostaglandin drug.
Methods :
Study consisted of 28 patients and 5 visits: screening/baseline visit and visits at 1.5, 3, 6 and 12 months after the medication switch from preserved latanoprost (Xalatan®) to preservative-free tafluprost (Taflotan®). Clinical evaluation and tear collection using Schirmer’s strips were performed during each visit. Relative quantification of tear proteins was done by NanoLC-TripleMSTOF using SWATH. Statistical and MS data analysis were performed with extensive software by Sciex, R software and Ingenuity pathway analysis (IPA).
Results :
SWATH library for 978 proteins was created and 785 proteins were relatively quantified in each sample. We compared protein expression data between the visits and identified 3 distinctive protein clusters with high reliability (p≥0.001). One of the clusters consisted of beneficial (lacrimal gland secreted proteins) ocular surface biomarkers, e.g. LYZ, PROL1 and various cystatins. Another two clusters included well-known inflammation related proteins such as ALB, TF and S100A8 and C3, ENO1 and S100A9. Further analysis of the clusters revealed 41 differentially expressed proteins (adjusted p-value < 0.05). Pathway analysis identified ‘inflammation of organ’ as the most enriched function term (p-value = 1.20E-05).
Conclusions :
Proteomic analysis stratified patients into three different groups. Two of them showed improvement of tear protein profile while one group showed increase in inflammatory related proteins. In the future, selected protein profiles could be used for the prediction of best therapeutic options for glaucoma patient.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.