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      Clinical impact of inflammation in dry eye disease: proceedings of the ODISSEY group meeting

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          Abstract

          Dry eye disease ( DED) is a common, multifactorial ocular condition with major impact on vision and quality of life. It is now well recognized that the pathophysiology of chronic DED can include a cycle of inflammation involving both innate and adaptive immune responses. Recently, in vitro/in vivo models have been used to obtain a better understanding of DED‐related inflammatory processes at molecular/cellular levels although they do not truly reproduce the complex and chronic hallmarks of human DED. In clinical DED research, advanced techniques such as impression cytology, conjunctival biopsy, in vivo confocal microscopy and multiplex tear analyses have allowed an improved assessment of inflammation in DED patients. This was supported by the identification of reliable inflammatory markers including matrix metalloproteinase‐9, human leucocyte antigen‐ DR or intercellular adhesion molecule‐1 in tears and impression cytology samples. One of the current therapeutic strategies focuses on breaking the inflammatory cycle perpetuating the ocular surface disease, and preclinical/clinical research has led to the development of promising anti‐inflammatory compounds. For instance, cyclosporine, already approved in the United States, has recently been authorized in Europe to treat DED associated with severe keratitis. In addition, other agents such as corticosteroids, doxycycline and essential fatty acids, through their anti‐inflammatory properties, show encouraging results. We now have a clearer understanding of the inflammatory processes involved in DED, and there is hope that the still emerging preclinical/clinical findings will be translated into new and highly effective therapies for patients in the near future.

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          The epidemiology of dry eye disease: report of the Epidemiology Subcommittee of the International Dry Eye WorkShop (2007).

          (2007)
          The report of the Epidemiology Subcommittee of the 2007 Dry Eye WorkShop summarizes current knowledge on the epidemiology of dry eye disease, providing prevalence and incidence data from various populations. It stresses the need to expand epidemiological studies to additional geographic regions, to incorporate multiple races and ethnicities in future studies, and to build a consensus on dry eye diagnostic criteria for epidemiological studies. Recommendations are made regarding several characteristics of dry eye questionnaires that might be suitable for use in epidemiological studies and randomized controlled clinical trials. Risk factors for dry eye and morbidity of the disease are identified, and the impact of dry eye disease on quality of life and visual function are outlined. Suggestions are made for further prospective research that would lead to improvement of both eye and general public health.
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            The pathophysiology, diagnosis, and treatment of dry eye disease.

            Dry eye disease (DED) is common; its prevalence around the world varies from 5% to 34%. Its putative pathogenetic mechanisms include hyperosmolarity of the tear film and inflammation of the ocular surface and lacrimal gland. Dry eye is clinically subdivided into two subtypes: one with decreased tear secretion (aqueous-deficient DED), and one with increased tear evaporation (hyperevaporative DED).
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              Experimental dry eye stimulates production of inflammatory cytokines and MMP-9 and activates MAPK signaling pathways on the ocular surface.

              To evaluate whether experimentally induced dry eye in mice activates mitogen-activated protein kinase (MAPK) signaling pathways, c-Jun N-terminal kinases (JNK), extracellular-regulated kinases (ERK), and p38 and stimulates ocular surface inflammation. 129SvEv/CD-1 mixed mice aged 6 to 8 weeks were treated with systemic scopolamine and exposure to an air draft for different lengths of time, from 4 hours to 10 days. Untreated mice were used as the control. The concentrations of IL-1beta and TNF-alpha in tear fluid washings and in corneal and conjunctival epithelia were measured by ELISA. MMP-9 in tear washings was evaluated by zymography, and gelatinase activity in the cornea and conjunctiva was determined by in situ zymography. Corneal and conjunctival epithelia were lysed in RIPA buffer for Western blot with MAPK antibodies, or they were lysed in 4 M guanidium thiocyanate solution for extraction of total RNA, which was used to determine gene expression by semiquantitative RT-PCR, real-time PCR, and gene array. Compared with those in age-matched control subjects, the concentrations of IL-1beta and MMP-9 in tear fluid washings and the concentrations of IL-1beta and TNF-alpha and gelatinolytic activity in the corneal and conjunctival epithelia were significantly increased in mice receiving treatments to induce dry eye after 5 or 10 days. The expression of IL-1beta, TNF-alpha, and MMP-9 mRNA by the corneal and conjunctival epithelia was also stimulated in mice treated for 5 or 10 days. The levels of phosphorylated JNK1/2, ERK1/2, and p38 MAPKs in the corneal and conjunctival epithelia were markedly increased as early as 4 hours after treatment, and they remained elevated up to 5 days. Experimental dry eye stimulates expression and production of IL-1beta, TNF-alpha, and MMP-9 and activates MAPK signaling pathways on the ocular surface. MAPKs are known to stimulate the production of inflammatory cytokines and MMPs, and they could play an important role in the induction of these factors that have been implicated in the pathogenesis of dry eye disease.
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                Author and article information

                Contributors
                cbaudouin@15-20.fr
                Journal
                Acta Ophthalmol
                Acta Ophthalmol
                10.1111/(ISSN)1755-3768
                AOS
                Acta Ophthalmologica
                John Wiley and Sons Inc. (Hoboken )
                1755-375X
                1755-3768
                08 April 2017
                March 2018
                : 96
                : 2 ( doiID: 10.1111/aos.2018.96.issue-2 )
                : 111-119
                Affiliations
                [ 1 ] Centre Hospitalier National d'Ophtalmologie des Quinze‐Vingts INSERM‐DHOS CIC 503 Paris France
                [ 2 ] UPMC Université Paris 06 UMR‐S968 Institut de la Vision Paris France
                [ 3 ] CNRS UMR‐7210 Paris France
                [ 4 ] Ambroise Paré Hospital, APHP Dept Ophthalmology F‐92100 Boulogne France
                [ 5 ] University of Versailles Saint Quentin en Yvelines 78000, Versailles France
                [ 6 ] Hacettepe University School of Medicine Ankara Turkey
                [ 7 ] Department of Ophthalmology Ludwig‐Maximilians University Munich Germany
                [ 8 ] Hospital Universitario Puerta de Hierro Madrid Spain
                [ 9 ] University Campus Bio‐Medico Rome Italy
                [ 10 ] Department of Ophthalmology Royal Victoria Infirmary and Newcastle University Newcastle upon Tyne UK
                [ 11 ] Department of Ophthalmology Heinrich Heine University Düsseldorf Germany
                [ 12 ] South Paris University Kremlin‐Bicêtre Paris France
                [ 13 ] Department of Ophthalmology Georgetown University Washington USA
                [ 14 ] University of Genoa Genoa Italy
                [ 15 ] St. Eriks Eye Hospital Stockholm Sweden
                [ 16 ] University of Messina Messina Italy
                Author notes
                [*] [* ] Correspondence:

                Christophe Baudouin, MD, PhD

                Centre Hospitalier National d'Ophtalmologie des Quinze‐Vingts

                28 rue de Charenton

                75012 Paris

                France

                Tel: +33 1 40 02 13 06

                Fax: +33 1 40 02 13 99

                Email: cbaudouin@ 12345615-20.fr

                Article
                AOS13436
                10.1111/aos.13436
                5836968
                28390092
                9b094480-2128-4465-989c-1a0b776ec429
                © 2017 The Authors Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 08 July 2016
                : 05 February 2017
                Page count
                Figures: 2, Tables: 0, Pages: 9, Words: 8555
                Funding
                Funded by: Santen
                Categories
                Review Article
                Review Articles
                Custom metadata
                2.0
                aos13436
                March 2018
                Converter:WILEY_ML3GV2_TO_NLMPMC version:version=5.3.2.2 mode:remove_FC converted:05.03.2018

                Ophthalmology & Optometry
                cytokines,dry eye disease,hla‐dr,hyperosmolarity,inflammation
                Ophthalmology & Optometry
                cytokines, dry eye disease, hla‐dr, hyperosmolarity, inflammation

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