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      Comparative analysis of cytokine profiles of glaucomatous tears and aqueous humour reveals potential biomarkers for trabeculectomy complications

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          Abstract

          Glaucoma is a multifactorial neurodegenerative disease that causes impaired vision and, in advanced cases, blindness. The increasing prevalence of glaucoma due to an ageing population has necessitated the identification of suitable biomarkers for the early detection of the disease. Aqueous humour ( AH) has been proposed as a source of biomarkers, but it can only be collected using a minor, yet invasive surgical intervention. Tears, however, are constantly available and can be collected any time via noninvasive methods. In order to examine the utility of tear as a surrogate for aqueous humour in biomarker development, we compared the levels of 27 cytokines and chemokines in paired samples of tear and aqueous humour using a Luminex multiplex immunobead‐based technique. Significantly higher levels of cytokines in tear compared to aqueous humour were detected suggesting that tear and aqueous humour are not identical in terms of inflammation response. Furthermore, the levels of IFN‐γ, GMCSF and IL‐5 in tear were significantly lower in patients who developed complications after one year, but no statistically significant changes in cytokine levels were observed in aqueous humour. These three molecules may have potential as predictive biomarkers for the appearance of late flap‐related complications of trabeculectomy.

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          Glaucoma is second leading cause of blindness globally

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            The anti-inflammatory and anti-angiogenic role of mesenchymal stem cells in corneal wound healing following chemical injury.

            To investigate the anti-inflammatory and anti-angiogenic effects of mesenchymal stem cells (MSC) in the chemically burned corneas, we mechanically removed the corneal epithelium of rats after 100% alcohol instillation. The rats were then randomized into four groups: fresh media, conditioned media derived from the MSC culture (MSC-CM), MSC applied topically to the damaged corneas for 2 hours immediately after the injury or MSC-CM applied either once or 3 times per day for 3 consecutive days. Corneal surface was evaluated every week. After 3 weeks, the corneas were stained with the hematoxylin-eosin, and the expression of interleukin (IL)-2, interferon (IFN)-gamma, IL-6, IL-10, transforming growth factor (TGF)-beta1, thrombospondin-1 (TSP-1), matrix metalloproteinase-2 (MMP-2), and vascular endothelial growth factor (VEGF) were analyzed. CD4+ cells were assessed in the corneas. We found that both MSC and three-time applied MSC-CM (1) reduced corneal inflammation and neovascularization, (2) decreased IL-2 and IFN-gamma, although increased IL-10 and TGF-beta1 as well as IL-6, (3) reduced the infiltration of CD4+ cells, and (4) upregulated the expression of TSP-1, although downregulated that of MMP-2. Interestingly, whereas three-time application of MSC-CM was partially effective, transplantation of MSC achieved a better outcome in suppressing corneal inflammation. The results of this study suggest that the anti-inflammatory and anti-angiogenic action of MSC in the chemically burned corneas might be mediated in part through paracrine pathways involving soluble factors such as IL-10, TGF-beta1, IL-6 and TSP-1.
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              Tear fluid biomarkers in ocular and systemic disease: potential use for predictive, preventive and personalised medicine

              In the field of predictive, preventive and personalised medicine, researchers are keen to identify novel and reliable ways to predict and diagnose disease, as well as to monitor patient response to therapeutic agents. In the last decade alone, the sensitivity of profiling technologies has undergone huge improvements in detection sensitivity, thus allowing quantification of minute samples, for example body fluids that were previously difficult to assay. As a consequence, there has been a huge increase in tear fluid investigation, predominantly in the field of ocular surface disease. As tears are a more accessible and less complex body fluid (than serum or plasma) and sampling is much less invasive, research is starting to focus on how disease processes affect the proteomic, lipidomic and metabolomic composition of the tear film. By determining compositional changes to tear profiles, crucial pathways in disease progression may be identified, allowing for more predictive and personalised therapy of the individual. This article will provide an overview of the various putative tear fluid biomarkers that have been identified to date, ranging from ocular surface disease and retinopathies to cancer and multiple sclerosis. Putative tear fluid biomarkers of ocular disorders, as well as the more recent field of systemic disease biomarkers, will be shown.
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                Author and article information

                Contributors
                cseva@med.unideb.hu
                Journal
                FEBS Open Bio
                FEBS Open Bio
                10.1002/(ISSN)2211-5463
                FEB4
                FEBS Open Bio
                John Wiley and Sons Inc. (Hoboken )
                2211-5463
                23 April 2019
                May 2019
                : 9
                : 5 ( doiID: 10.1002/feb4.2019.9.issue-5 )
                : 1020-1028
                Affiliations
                [ 1 ] Biomarker Research Group Department of Biochemistry and Molecular Biology Faculty of Medicine University of Debrecen Hungary
                [ 2 ] Proteomics Core Facility Department of Biochemistry and Molecular Biology Faculty of Medicine University of Debrecen Hungary
                [ 3 ] Department of Ophthalmology Faculty of Medicine University of Debrecen Hungary
                [ 4 ] Clinica Oculistica DiNOGMI University of Genoa and IRCCS Ospedale Policlinico San Martino Genova Italy
                Author notes
                [*] [* ] Correspondence

                É. Csősz, Biomarker Research Group, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

                Tel: +36 52 416432

                E‐mail: cseva@ 123456med.unideb.hu

                Author information
                https://orcid.org/0000-0003-4373-2175
                Article
                FEB412637
                10.1002/2211-5463.12637
                6487689
                30959565
                f9ebd296-0bf7-4232-bf71-4351c49370b7
                © 2019 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 11 February 2019
                : 11 March 2019
                : 05 April 2019
                Page count
                Figures: 2, Tables: 1, Pages: 9, Words: 5765
                Funding
                Funded by: János Bolyai Research Scholarship of the Hungarian Academy of Sciences
                Award ID: PD116817
                Award ID: PD121075
                Award ID: ÚNKP-18-4-DE-436
                Funded by: National Research, Development and Innovation Office
                Categories
                Research Article
                Research Articles
                Custom metadata
                2.0
                feb412637
                May 2019
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.6.2.1 mode:remove_FC converted:29.04.2019

                aqueous humour,biomarker,cytokine profile,glaucoma,tear,trabeculectomy

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