7
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Comparison of the Anti-Inflammatory Effects of Artificial Tears in a Rat Model of Corneal Scraping

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Purpose: Artificial tears (ATs) are used routinely to alleviate the symptoms of mild to moderate dry eye. Preservative-free cationic emulsions (eg, Cationorm ®) are an innovative approach for the management of signs and symptoms of dry eye. The aim of the present exploratory experiment was to evaluate the efficacy of this cetalkonium chloride (CKC)-containing cationic emulsion on debrided cornea and to characterize its effects on scraping-induced inflammation.

          Methods: Four ATs were assessed in a rat model of corneal scraping. The upper part of the corneal epithelium was scraped before a 5-day treatment, followed by clinical evaluations and fluorescein staining to evaluate cornea recovery. The anti-inflammatory efficacy of the ATs was assessed in vivo and in vitro.

          Results: In vivo confocal microscopy (IVCM) revealed a trend toward better corneal clinical signs (lower IVCM scores) for the animals treated with the unpreserved ATs. Benzalkonium chloride treatment decreased goblet cell count by 37.5%. While the soft-preserved Systane Balance ® and Optive ® and the preservative-free Vismed ® had no effect on the goblet cell count, Cationorm increased this count by almost 40%. Interestingly, inflammatory cell infiltration in the stroma was at its lowest following treatment with the preservative-free Cationorm. Cationorm is also the only AT decreasing IL6- and IL8-stimulated secretion by 59% and 74%, respectively.

          Conclusion: By restoring an adequately hydrated ocular surface environment, the different ATs promote corneal epithelium healing. These data position Cationorm as a promising AT for the management of signs and symptoms of dry eye in patients with mild to moderate dry eye disease presenting chronic subclinical levels of ocular inflammation.

          Related collections

          Most cited references63

          • Record: found
          • Abstract: found
          • Article: not found

          Preservatives in eyedrops: the good, the bad and the ugly.

          There is a large body of evidence from experimental and clinical studies showing that the long-term use of topical drugs may induce ocular surface changes, causing ocular discomfort, tear film instability, conjunctival inflammation, subconjunctival fibrosis, epithelial apoptosis, corneal surface impairment, and the potential risk of failure for further glaucoma surgery. Subclinical inflammation has also been described in patients receiving antiglaucoma treatments for long periods of time. However, the mechanisms involved, i.e., allergic, toxic, or inflammatory, as well as the respective roles of the active compound and the preservative in inducing the toxic and/or proinflammatory effects of ophthalmic solutions, is still being debated. The most frequently used preservative, benzalkonium chloride (BAK), has consistently demonstrated its toxic effects in laboratory, experimental, and clinical studies. As a quaternary ammonium, this compound has been shown to cause tear film instability, loss of goblet cells, conjunctival squamous metaplasia and apoptosis, disruption of the corneal epithelium barrier, and damage to deeper ocular tissues. The mechanisms causing these effects have not been fully elucidated, although the involvement of immunoinflammatory reactions with the release of proinflammatory cytokines, apoptosis, oxidative stress, as well as direct interactions with the lipid components of the tear film and cell membranes have been well established. Preservative-induced adverse effects are therefore far from being restricted to only allergic reactions, and side effects are often very difficult to identify because they mostly occur in a delayed or poorly specific manner. Care should therefore be taken to avoid the long-term use of preservatives, otherwise a less toxic alternative to BAK should be developed, as this weakly allergenic but highly toxic compound exerts dose- and time-dependent effects. On the basis of all these experimental and clinical reports, it would be advisable to use benzalkonium-free solutions whenever possible, especially in patients with the greatest exposure to high doses or prolonged treatments, in those suffering from preexisting or concomitant ocular surface diseases, and those experiencing side effects related to the ocular surface. Indeed, mild symptoms should not be underestimated, neglected, or denied, because they may very well be the apparent manifestations of more severe, potentially threatening subclinical reactions that may later cause major concerns. Copyright (c) 2010 Elsevier Ltd. All rights reserved.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Hyaluronan fragments act as an endogenous danger signal by engaging TLR2.

            Upon tissue injury, high m.w. hyaluronan (HA), a ubiquitously distributed extracellular matrix component, is broken down into lower m.w. (LMW) fragments, which in turn activate an innate immune response. In doing so, LMW HA acts as an endogenous danger signal alerting the immune system of a breach in tissue integrity. In this report, we demonstrate that LMW HA activates the innate immune response via TLR-2 in a MyD88-, IL-1R-associated kinase-, TNFR-associated factor-6-, protein kinase Czeta-, and NF-kappaB-dependent pathway. Furthermore, we show that intact high m.w. HA can inhibit TLR-2 signaling. Finally, we demonstrate that LMW HA can act as an adjuvant promoting Ag-specific T cell responses in vivo in wild-type but not TLR-2(null) mice.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              The core mechanism of dry eye disease is inflammation.

              The purpose of this article is to review the evidence for the hypothesis that the core mechanism of dry eye disease (DED) is inflammation, including evidence from recent basic, clinical, and translational research involving human patients, animal models, and cell cultures.
                Bookmark

                Author and article information

                Journal
                J Ocul Pharmacol Ther
                J Ocul Pharmacol Ther
                jop
                Journal of Ocular Pharmacology and Therapeutics
                Mary Ann Liebert, Inc. (140 Huguenot Street, 3rd FloorNew Rochelle, NY 10801USA )
                1080-7683
                1557-7732
                01 March 2016
                01 March 2016
                : 32
                : 2
                : 109-118
                Affiliations
                [ 1 ]Novagali Innovation Center , Santen SAS, Evry, France.
                [ 2 ]Iris Pharma, La Gaude, France.
                Author notes
                Address correspondence to: Dr. Jean-Sébastien Garrigue, Novagali Innovation Center Santen SAS, 1, rue Pierre Fontaine, Bâtiment Genavenir IV, F-91058 Evry Cedex, France

                E-mail: jean-sebastien.garrigue@ 123456santen.fr
                Article
                10.1089/jop.2015.0054
                10.1089/jop.2015.0054
                4779975
                26751507
                8b1d5fd7-8559-4f59-ae54-056c84b8e7ec
                © Daull et al. 2016; Published by Mary Ann Liebert, Inc.

                This Open Access article is distributed under the terms of the Creative Commons Attribution Noncommercial License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.

                History
                : 18 May 2015
                : 19 October 2015
                Page count
                Figures: 4, Tables: 1, References: 71, Pages: 10
                Categories
                Original Articles

                Comments

                Comment on this article