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      Interactions of Meibum and Tears with Mucomimetic Polymers: A Hint towards the Interplay between the Layers of the Tear Film

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          Abstract

          Recent clinical findings suggest that mucomimetic polymers (MMP) can alter not only the texture of the aqueous tear but also the spreading and structure of the tear film (TF) lipid layer, thereby allowing for their synchronized performance in vivo. Thus, we aimed to evaluate in vitro (i) the capability of pharmaceutically applicable MMP to ensure the formation of post-evaporative ferning patterns (a characteristic feature of the “healthy” tear colloid) and (ii) the MMP interactions with human meibum films accessed in the course of blink-like deformations via Langmuir surface balance and Brewster angle microscopy (BAM). Four MMP were used- hyaluronic acid (HA), cross-linked hyaluronic acid (CHA), carboxymethyl cellulose (CMC) and gellan gum (GG)- at the concentrations of 0.0001%, 0.001%, 0.01%, 0.05% and 0.1%. Significant differences were observed in the MMP fern formation capability: CHA (≥0.001%) > HA (≥0.01%) = CMC (≥0.01%) > GG (≥0.05%). All MMP affected the spreading of meibum, with BAM micrographs revealing thickening of the films. CHA was particularly efficient, showing concentration-dependent enhancement of tear ferning and of meibomian layer structure, surfactant properties and viscoelasticity. Thus, endogenous and exogenous MMP may play key roles for the concerted action of the TF layers at the ocular surface, revealing novel routes for TF-oriented therapeutic applications.

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          Most cited references46

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          TFOS DEWS II Tear Film Report

          The members of the Tear Film Subcommittee reviewed the role of the tear film in dry eye disease (DED). The Subcommittee reviewed biophysical and biochemical aspects of tears and how these change in DED. Clinically, DED is characterized by loss of tear volume, more rapid breakup of the tear film and increased evaporation of tears from the ocular surface. The tear film is composed of many substances including lipids, proteins, mucins and electrolytes. All of these contribute to the integrity of the tear film but exactly how they interact is still an area of active research. Tear film osmolarity increases in DED. Changes to other components such as proteins and mucins can be used as biomarkers for DED. The Subcommittee recommended areas for future research to advance our understanding of the tear film and how this changes with DED. The final report was written after review by all Subcommittee members and the entire TFOS DEWS II membership.
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            Hyaluronic Acid in Inflammation and Tissue Regeneration.

            Hyaluronic acid (HA), the main component of extracellular matrix, is considered one of the key players in the tissue regeneration process. It has been proven to modulate via specific HA receptors, inflammation, cellular migration, and angiogenesis, which are the main phases of wound healing. Studies have revealed that most HA properties depend on its molecular size. High molecular weight HA displays anti-inflammatory and immunosuppressive properties, whereas low molecular weight HA is a potent proinflammatory molecule. In this review, the authors summarize the role of HA polymers of different molecular weight in tissue regeneration and provide a short overview of main cellular receptors involved in HA signaling. In addition, the role of HA in 2 major steps of wound healing is examined: inflammation and the angiogenesis process. Finally, the antioxidative properties of HA are discussed and its possible clinical implication presented.
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              Hyaluronan: molecular size‐dependent signaling and biological functions in inflammation and cancer

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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                09 March 2021
                March 2021
                : 22
                : 5
                : 2747
                Affiliations
                [1 ]Department of Cytology, Histology and Embryology, Faculty of Biology, St. Kliment Ohridski University of Sofia, 8 Dragan Tzankov Blvd., 1164 Sofia, Bulgaria; peftimov@ 123456uni-sofia.bg
                [2 ]Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan; nyokoi@ 123456koto.kpu-m.ac.jp
                [3 ]Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, 1649-004 Lisbon, Portugal; anammelo@ 123456tecnico.ulisboa.pt
                [4 ]Novagali Innovation Center, Santen SAS, 91058 Evry, France; philippe.daull@ 123456santen.com
                Author notes
                [* ]Correspondence: georgi.georgiev@ 123456tecnico.ulisboa.pt ; Tel.: +351-218-419-065
                Author information
                https://orcid.org/0000-0002-2086-5939
                Article
                ijms-22-02747
                10.3390/ijms22052747
                7963170
                33803116
                70b84b40-4ddb-46e0-aa40-59a115db2a0e
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 18 January 2021
                : 03 March 2021
                Categories
                Article

                Molecular biology
                mucomimetic polymers,cross-linked hyaluronic acid,tear film,ferning patterns,human meibum,surface properties

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