DOCSLIB.ORG

Emerging Targets of Inflammation and Tear Secretion in Dry Eye Disease

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Emerging Targets of Inflammation and Tear Secretion in Dry Eye Disease Drug Discovery Today Volume 24, Number 8 August 2019 PERSPECTIVE feature Emerging targets of inflammation and tear secretion in dry eye disease Maria Markoulli, [email protected] and Alex Hui The underlying mechanisms of dry eye are thought to be part of a vicious circle involving a hyperosmolarity-triggered inflammatory cascade, resulting in loss of goblet cells and glycocalyx mucin and observed corneal and conjunctival epithelial cell damage. This damage leads to increased tear film instability, further hyperosmolarity and hence perpetuating of a vicious circle. The aim of dry eye management is to restore the homeostasis of the tear film and break the perpetuation of this vicious circle. Despite the plethora of treatment options available, many of these are largely palliative, short-lived and require repeated instillations. Two emerging areas in dry eye therapy aim PERSPECTIVE to promote tear secretion and to safely manage dry eye-associated inflammation and are the focus of this review. Features Dry eye disease and its treatment into aqueous deficiency and evaporative dry Promoting tear secretion Dry eye disease is defined by the Tear Film and eye, but it is now understood that both con- Topical pharmaceutical secretagogues Ocular Surface Dry Eye Workshop (TFOS DEWS) ditions lie on a continuum that can be present Secretagogues stimulate the secretion of the II as ``a multifactorial disease of the ocular simultaneously to a varying degree [1]. aqueous, mucin or lipid constituents of the tear surface characterized by a loss of homeostasis The aim of dry eye management is to restore film, hence minimising the impact of tear film of the tear film, and accompanied by ocular the homeostasis of the tear film and break the instability and goblet cell and glycocalyx mucin symptoms, in which tear film instability and perpetuation of the dry eye circle [3]. Current loss that form part of the vicious circle of dry eye hyperosmolarity, ocular surface inflammation treatments can be largely categorized into one disease [2]. The following discussion separates and damage, and neurosensory abnormalities of six categories: treatment for aqueous defi- secretagogues into those that stimulate each of play etiological roles” [1]. The underlying ciency, treatment for meibomian gland dys- these constituents, however it should be rec- mechanisms of dry eye are thought to be part function and eyelid abnormalities, anti- ognized the potential for overlapping effects of a vicious circle involving a hyperosmolarity- inflammatory therapy, surgical approaches, di- affecting multiple components of the tear film. triggered inflammatory cascade, resulting in etary modifications and environmental modifi- loss of goblet cells and glycocalyx mucin and cations [3]. Despite the plethora of treatment Aqueous secretagogues observed corneal and conjunctival epithelial options available, many of these are largely Diquafosol tetrasodium (3% ophthalmic solu- 1 cell damage [2]. This damage to the ocular palliative, short-lived and require repeated tion, Diquas ; Santen, Osaka, Japan) is ap- surface leads to increased tear film instability, instillations [4]. Two emerging areas in dry eye proved for use in Japan and South Korea. This is further feeding tear hyperosmolarity and hence therapy aim to promote tear secretion and to a mucolytic compound and a purinergic P2Y2 perpetuating the vicious circle [2] (Fig. 1). Tra- safely manage dry eye-associated inflammation receptor agonist that stimulates tear fluid and ditionally, the disease has been characterized (Fig. 1) and are the focus of this review. mucin secretion [5,6]. P2Y receptors are meta- 1359-6446/ã 2019 Elsevier Ltd. All rights reserved. https://doi.org/10.1016/j.drudis.2019.02.006 www.drugdiscoverytoday.com 1427 PERSPECTIVE Drug Discovery Today Volume 24, Number 8 August 2019 Tear hyperosmolarity A cascade of signaling events within surface epithelial cells Tear film LFA-1 Vicious circle instability antagonists of dry eye IL-1, 17 IFNγ TNFα+ MMPs Lipid, aqueous, Goblet cell and mucus glycocalyx mucin loss secretagogues epithelial damage -apoptosis Drug Discovery Today FIGURE 1 The vicious circle of dry eye disease (adapted from Bron, A.J. et al. (2017) TFOS DEWS II pathophysiology report. Ocul Surf 15 (3), 438–510) [1]. The core mechanisms of dry eye disease are thought to be tear hyperosmolarity which leads to a cascade of signalling events within epithelial cells. This leads to inflammation which further leads to ocular surface damage and tear film instability. Without intervention, this circle is thought to be self-perpetuating. The proposed actions of the two emerging treatments for dry eye disease presented in this review, secretagogues and lymphocyte function-associated antigen-1 antagonists (LFA-1 antagonists) on this cycle are shown in the blue. IL: interleukin, IFNF: interferon gamma, TNFa: tumor necrosis factor alpha, MMPs: matrix metalloproteinases. botropic guanosine triphosphate binding pro- resulted in an improved fluorescein staining contact lens-related dry eye disease [33]. In the tein (G-protein) coupled receptors and P2Y2 score similar to the control group that was presence of ocular surface inflammation, lacritin receptors specifically activate phospholipase C- taking 0.1% sodium hyaluronate ophthalmic is down-regulated by tear tissue transgluta- b [7]. These receptors are found at the corneal solution, and even further improvements in rose minase which is elevated in dry eye disease Features epithelium, the conjunctival epithelium, the bengal staining, more so than the control [12]. In [34,35]. Lacritin’s application in dry eye disease is goblet cells and meibomian glands [8]. In age- a prospective study evaluating 3% diquafosol aimed at taking advantage of tear proteins as related dry eye mice models, use of diquafosol sodium on 13 patients over a 3-month period, an potential biotherapeutics. In mice models of PERSPECTIVE results in increased goblet cell density and a improvement in meibomian gland appearance Sjögren’s Syndrome treated with lacritin, treat- decrease in ocular surface inflammation [9]. and function and symptoms was found [17]. In a ment with lacritin demonstrated a 46% increase Byun et al. demonstrated that diquafosol study of 15 patients with aqueous deficient dry in tear secretion and a reduction in lissamine accelerates corneal epithelial wound healing eye disease treated for 6 months, an improve- green staining, compared to the control eyes possibly as a result of epidermal growth factor ment in symptoms, corneal staining, tear break- [32]. On the cornea it also resulted in a shift from receptor/extracellular signal-regulated kinase up time and tear meniscus height was noted skin-specific cytokeratin to K12, a corneal-spe- stimulated cell proliferation and migration [10]. after 1 month and maintained for the 6-month cific cytokeratin that is abundant in the healthy Other studies have shown effects of the drug to observation period [18]. Other studies have ocular mucosal epithelium [32]. The drug is suppress the loss of corneal epithelial integrity supported similar findings for diquafosol’s im- currently not available commercially although it [6,11]. pact on the ocular surface, showing an im- is being evaluated for its safety and efficacy in an Several randomized controlled clinical trials provement in symptoms and corneal staining ongoing human clinical trial (NCT03226444), have demonstrated the efficacy and safety of [19], tear volume [20,21], lid margin abnormal- with an estimated 201 participants randomised TM diquafosol administered topically for dry eye ities including vascularity [22], corneal staining to receive either 0.005% or 0.01% Lacripep , or disease [12–14]. In a 4-week randomised, dou- [23,22], meibomian gland function [22] and lipid placebo [36]. ble-masked study of 286 patients with dry eye layer thickness [24]. Diquafosol’s ability to disease comparing diquafosol 3% to sodium improve higher order aberrations has been Mucin secretagogues 1 hyaluronate ophthalmic solution, each taken 6 reported, but other studies have contradicted Rebamipide ophthalmic suspension (Mucosta ; times daily for 4 weeks, diquafosol significantly this, suggesting its impact on this parameter to Otsuka Pharmaceutical, Chiyoda, Japan) is a improved conjunctival staining scores while be equivocal [25–29]. There have also been little mucin secretagogue that promotes the pro- having a similar adverse event profile as the to no studies on the long-term usage of this duction of mucin-like glycoproteins in human sodium hyaluronate [15]. Combining these two agent and it currently remains unavailable to corneal epithelial cells [37] as well as the ex- products has been shown to be effective in most areas within the world. pression of membrane-associated mucins stabilizing vision and dry eye symptoms fol- Lacritin is a tear glycoprotein prosecretory MUC1, MUC4 and MUC16 [37]. Currently in lowing LASIK [16]. In a randomized, parallel- mitogen that promotes basal tear secretion [30] Japan, along with hyaluronic acid and diqua- group comparison study of 497 patients with and epithelial homeostasis [31]. It is downre- fosol, it forms the mainstay of dry eye treatment dry eye disease over a 4-week period, diquafosol gulated in both Sjögren’s Syndrome [32] and [38]. Rebamipide was originally launched as an 1428 www.drugdiscoverytoday.com Drug Discovery Today Volume 24, Number 8 August 2019 PERSPECTIVE oral medication for the repair of gastric mucosa effects has since been shown
Load more

Recommended publications
  • Synthesis and Biological Evaluation of Purine and Pyrimidine Based Ligands for the A3 and the P2Y2 Purinergic Receptors
    Synthesis and Biological Evaluation of Purine and Pyrimidine Based Ligands for the A3 and the P2Y2 Purinergic Receptors Apr. Liesbet Cosyn Thesis submitted to the Faculty of Pharmaceutical Sciences to obtain the degree of Doctor in Pharmaceutical Sciences Promoter Prof. dr. apr. Serge Van Calenbergh Academic year 2007-2008 TABLE OF CONTENTS 1 INTRODUCTION ................................................................................................. 3 1.1 Purinergic Receptors ................................................................................. 3 1.2 Adenosine Analogues and the Adenosine A3 Receptor ......................... 4 1.2.1 Adenosine................................................................................................. 4 1.2.2 The Adenosine Receptors: G-protein-Coupled Receptors........................ 7 1.2.3 Adenosine Receptor Subtypes and Their Signalling............................... 10 1.2.4 The Adenosine A3 Receptor ................................................................... 12 1.2.4.1 Adenosine A3 Receptor Agonists ................................................. 12 1.2.4.2 Adenosine A3 Receptor Antagonists ............................................ 16 1.2.4.3 Allosteric Modulation.................................................................... 21 1.2.4.4 Molecular Modeling of the Adenosine A3 Receptor...................... 22 1.2.4.5 The Neoceptor concept................................................................ 23 1.2.4.6 Therapeutic Potential of A3AR Agonists......................................
    [Show full text]
  • Regulation and Relevance for Chronic Lung Diseases
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Springer - Publisher Connector Purinergic Signalling (2006) 2:399–408 DOI 10.1007/s11302-006-9001-7 ORIGINAL ARTICLE E-NTPDases in human airways: Regulation and relevance for chronic lung diseases Lauranell H. Burch & Maryse Picher Received: 11 January 2005 /Accepted: 21 December 2005 / Published online: 30 May 2006 # Springer Science + Business Media B.V. 2006 Abstract Chronic obstructive lung diseases are char- are characterized by higher rates of nucleotide elimi- acterized by the inability to prevent bacterial infection nation, azide-sensitive E-NTPDase activities and ex- and a gradual loss of lung function caused by recurrent pression. This review integrates the biphasic regulation inflammatory responses. In the past decade, numerous of airway E-NTPDases with the function of purine studies have demonstrated the importance of nucleo- signaling in lung diseases. During acute insults, a tide-mediated bacterial clearance. Their interaction transient reduction in E-NTPDase activities may be with P2 receptors on airway epithelia provides a rapid beneficial to stimulate ATP-mediated bacterial clear- Fon-and-off_ signal stimulating mucus secretion, cilia ance. In chronic lung diseases, elevating E-NTPDase beating activity and surface hydration. On the other activities may represent an attempt to prevent P2 hand, abnormally high ATP levels resulting from receptor desensitization and nucleotide-mediated lung damaged epithelia and bacterial lysis may cause lung damage. edema and exacerbate inflammatory responses. Air- way ATP concentrations are regulated by ecto nucle- Keywords apyrase . bacterial clearance . CD39 . oside triphosphate diphosphohydrolases (E-NTPDases) chronic obstructive lung diseases .
    [Show full text]
  • P2X7 Receptor-Induced CD23 Shedding from B Cells Aleta Pupovac University of Wollongong, [email protected]
    University of Wollongong Research Online University of Wollongong Thesis Collection University of Wollongong Thesis Collections 2014 P2X7 receptor-induced CD23 shedding from B cells Aleta Pupovac University of Wollongong, [email protected] Research Online is the open access institutional repository for the University of Wollongong. For further information contact the UOW Library: [email protected] P2X7 receptor-induced CD23 shedding from B cells A thesis submitted in fulfilment of the requirements for the award of the degree Doctor of Philosophy from UNIVERSITY OF WOLLONGONG by Aleta Pupovac Bachelor of Biotechnology (Adv) (Hons) Illawarra Health and Medical Research Institute School of Biological Sciences 2014 THESIS CERTIFICATION I, Aleta Pupovac, declare that this thesis, submitted in fulfilment of the requirements for the award of Doctor of Philosophy, in the Department of Biological Sciences, University of Wollongong, is wholly my own work unless otherwise referenced or acknowledged. The document has not been submitted for qualifications at any other academic institution. Aleta Pupovac 2014 i ACKNOWLEDGEMENTS I would like to thank my supervisor, Ron Sluyter, for providing me with the skills and patience to tackle science confidently in the future. Your knowledge, guidance and support were essential in the completion of this project, and have moulded me into the scientist that I always hoped to be. I will be forever grateful that you gave me the opportunity to be a part of your lab, and for your excellent supervision. A student cannot ask for a better supervisor. Also thanks to my co-supervisor Marie Ranson, for providing helpful advice over the years.
    [Show full text]
  • A Pilot Exome-Wide Association Study of Age-Related Cataract in Koreans
    Available online at www.jbr-pub.org Open Access at PubMed Central The Journal of Biomedical Research, 2016, 30(3):186-190 Original Article A pilot exome-wide association study of age-related cataract in Koreans Sang-Yong Eom1,2, Dong-Hyuk Yim1,2, Jung-Hyun Kim3, Joo-Byung Chae4, Yong-Dae Kim1,2, Heon Kim1,2, 1​Center for Farmer's Safety and Health, Chungbuk National University Hospital, Cheongju, Chungbuk 28644, Republic of Korea; 2​Department of Preventive Medicine, College of Medicine, Chungbuk National University, Cheongju, Chungbuk 28644, Republic of Korea; 3 Department of Optometry, Daejeon Health Science College, Daejeon 34504, Republic of Korea; 4 Department of Ophthalmology, College of Medicine, Chungbuk National University, Cheongju 28644, Republic of Korea. Abstract Age-related cataract (ARC) is the most common cause of visual impairment and blindness worldwide. A previous study reported that genetic factors could explain approximately 50% of the heritability of cataract. However, a genetic predisposition to ARC and the contributing factors have not yet been elucidated in the Korean population. In this study, we assessed the influence of genetic polymorphisms on the risk of ARC in Koreans, including 156 cataract cases and 138 healthy adults. We conducted an exome-wide association study using Illumina Human Exome-12v1.2 platform to screen 244,770 single nucleotide polymorphisms (SNPs). No SNPs reached exome-wide significance level of association (P < 1×10−6). B3GNT4 rs7136356 showed the most significant association with ARC (P = 6.54×10−5). Two loci (MUC16 and P2RY2) among the top 20 ARC-associated SNPs were recognized as probably linked to cata- ractogenesis.
    [Show full text]
  • P2Y Receptor Agonists for the Treatment of Dry
    Clinical Ophthalmology Dovepress open access to scientific and medical research Open Access Full Text Article REVIEW P2Y2 receptor agonists for the treatment of dry eye disease: a review Oliver C F Lau1 Abstract: Recent advances in the understanding of dry eye disease (DED) have revealed Chameen previously unexplored targets for drug therapy. One of these drugs is diquafosol, a uridine 1,2 nucleotide analog that is an agonist of the P2Y receptor. Several randomized controlled trials Samarawickrama 2 Simon E Skalicky1–3 have demonstrated that the application of topical diquafosol significantly improves objective markers of DED such as corneal and conjunctival fluorescein staining and, in some studies, 1Sydney Eye Hospital, Sydney, NSW, Australia; 2Save Sight Institute, tear film break-up time and Schirmer test scores. However, this has been accompanied by only University of Sydney, Sydney, partial improvement in patient symptoms. Although evidence from the literature is still relatively 3 NSW, Australia; Ophthalmology limited, early studies have suggested that diquafosol has a role in the management of DED. Department, Addenbrooke’s Hospital, Cambridge, United Kingdom Additional studies would be helpful to delineate how different subgroups of DED respond to diquafosol. The therapeutic combination of diquafosol with other topical agents also warrants further investigation. Keywords: dry eye disease, meibomian gland disease, aqueous tear deficiency, diquafosol, P2Y2 agonists Introduction Dry eye disease (DED) is a complex clinical entity characterized by symptoms of discomfort and visual disturbance. It is associated with tear film instability, increased tear film osmolarity, and ocular surface inflammation.1 It has a high prevalence that, depending on the population studied, varies from 5% to 35%.2,3 DED commonly causes symptoms including foreign body sensation, dryness, irritation, itching, and light sensitivity.4 It impacts patients’ daily life and function.
    [Show full text]
  • P2X and P2Y Receptors P2Y and P2X Tocris Bioscience Scientific Review Series
    P2X and P2Y Receptors Kenneth A. Jacobson Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Tel.: 301-496- 9024, Fax: 301-480-8422, E-mail: [email protected] Kenneth Jacobson serves as Chief of the Laboratory of Bioorganic Chemistry and the Molecular Recognition Section at the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health in Bethesda, Maryland, USA. Dr. Jacobson is a medicinal chemist with interests in the structure and pharmacology of G-protein- coupled receptors, in particular receptors for adenosine and for purine and pyrimidine nucleotides. Contents Subtypes and Structures of P2 Subtypes and Structures of P2 Receptor Families ........ 1 Receptor Families The P2 receptors for extracellular nucleotides are Pharmacological Probes for P2X Receptors .................. 3 widely distributed in the body and participate in 1,2 regulation of nearly every physiological process. DRIVING RESEARCH FURTHER Non-Selective P2X Ligands ............................................ 3 Of particular interest are nucleotide receptors in the immune, inflammatory, cardiovascular, muscular, P2X1 and P2X2 Receptors ............................................... 5 and central and peripheral nervous systems. The ubiquitous signaling properties of extracellular P2X3 Receptor ................................................................ 6 nucleotides acting at two
    [Show full text]
  • Anatomical Classification Guidelines V2021 EPHMRA ANATOMICAL CLASSIFICATION GUIDELINES 2021
    EPHMRA ANATOMICAL CLASSIFICATION GUIDELINES 2021 Anatomical Classification Guidelines V2021 "The Anatomical Classification of Pharmaceutical Products has been developed and maintained by the European Pharmaceutical Marketing Research Association (EphMRA) and is therefore the intellectual property of this Association. EphMRA's Classification Committee prepares the guidelines for this classification system and takes care for new entries, changes and improvements in consultation with the product's manufacturer. The contents of the Anatomical Classification of Pharmaceutical Products remain the copyright to EphMRA. Permission for use need not be sought and no fee is required. We would appreciate, however, the acknowledgement of EphMRA Copyright in publications etc. Users of this classification system should keep in mind that Pharmaceutical markets can be segmented according to numerous criteria." © EphMRA 2021 Anatomical Classification Guidelines V2021 CONTENTS PAGE INTRODUCTION A ALIMENTARY TRACT AND METABOLISM 1 B BLOOD AND BLOOD FORMING ORGANS 28 C CARDIOVASCULAR SYSTEM 36 D DERMATOLOGICALS 51 G GENITO-URINARY SYSTEM AND SEX HORMONES 58 H SYSTEMIC HORMONAL PREPARATIONS (EXCLUDING SEX HORMONES) 68 J GENERAL ANTI-INFECTIVES SYSTEMIC 72 K HOSPITAL SOLUTIONS 88 L ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS 96 M MUSCULO-SKELETAL SYSTEM 106 N NERVOUS SYSTEM 111 P PARASITOLOGY 122 R RESPIRATORY SYSTEM 124 S SENSORY ORGANS 136 T DIAGNOSTIC AGENTS 143 V VARIOUS 145 Anatomical Classification Guidelines V2021 INTRODUCTION The Anatomical Classification was initiated in 1971 by EphMRA. It has been developed jointly by Intellus/PBIRG and EphMRA. It is a subjective method of grouping certain pharmaceutical products and does not represent any particular market, as would be the case with any other classification system.
    [Show full text]
  • Synthesis and Biological Evaluation of Purine and Pyrimidine Based Ligands for the a 3 and the P2Y 2 Purinergic Receptors
    Synthesis and Biological Evaluation of Purine and Pyrimidine Based Ligands for the A 3 and the P2Y 2 Purinergic Receptors Apr. Liesbet Cosyn Thesis submitted to the Faculty of Pharmaceutical Sciences to obtain the degree of Doctor in Pharmaceutical Sciences Promoter Prof. dr. apr. Serge Van Calenbergh Academic year 2007-2008 TABLE OF CONTENTS 1 INTRODUCTION ................................................................................................. 3 1.1 Purinergic Receptors ................................................................................. 3 1.2 Adenosine Analogues and the Adenosine A 3 Receptor ......................... 4 1.2.1 Adenosine................................................................................................. 4 1.2.2 The Adenosine Receptors: G-protein-Coupled Receptors........................ 7 1.2.3 Adenosine Receptor Subtypes and Their Signalling............................... 10 1.2.4 The Adenosine A 3 Receptor ................................................................... 12 1.2.4.1 Adenosine A 3 Receptor Agonists ................................................. 12 1.2.4.2 Adenosine A 3 Receptor Antagonists ............................................ 16 1.2.4.3 Allosteric Modulation.................................................................... 21 1.2.4.4 Molecular Modeling of the Adenosine A 3 Receptor...................... 22 1.2.4.5 The Neoceptor concept................................................................ 23 1.2.4.6 Therapeutic Potential of A 3AR Agonists......................................
    [Show full text]
  • Thèse Version Finale 27 Mai 2011
    Faculté de Pharmacie Ecole Doctorale en Sciences Pharmaceutiques Contribution à l'étude des réponses cellulaires secondaires à l'activation de récepteurs purinergiques ionotropes dans les glandes salivaires et les macrophages de souris Michèle SEIL Thèse présentée en vue de l’obtention du grade de Docteur en Sciences Biomédicales et Pharmaceutiques Promoteur : Jean-Paul DEHAYE (Laboratoire de Chimie biologique et médicale et de Microbiologie pharmaceutique) Composition du jury : Pierre DUEZ (Président) Carine DE VRIESE (Secrétaire) Jean-Michel KAUFFMANN Hassan JIJAKLI Astrid VANDEN ABBEELE (Faculté de Médecine, Université libre de Bruxelles) Bernard ROBAYE (Faculté des Sciences, Université libre de Bruxelles) 2011 REMERCIEMENTS Je voudrais tout d’abord remercier mon promoteur, le Professeur Jean-Paul Dehaye pour m’avoir accueillie dans son laboratoire. Sa motivation, sa disponibilité, son expérience, ses connaissances scientifiques et ses nombreux conseils m’ont permis de mener à bien cette thèse. Je tiens à exprimer ma sincère gratitude au Professeur Stéphanie Pochet pour m’avoir formé aux différentes techniques de laboratoire, pour ses nombreux conseils, sa disponibilité et sa gentillesse. Je remercie le Dr. Michel Vandenbranden pour avoir réalisé les analyses infrarouge et pour ses conseils scientifiques. Je voudrais également exprimer mes remerciements au Professeur Nathalie Verbruggen pour m’avoir donnée accès au spectrophotomètre NanoDrop 2000c. Mes remerciements vont à tous les membres, anciens et actuels, du Département de Biopharmacie dont le Service de Chimie Biologique et Médicale et de Microbiologie Pharmaceutique. Je remercie en particulier Sara, Manuela et Robert pour leur aide lors des manipulations effectuées et pour les moments passés ensemble aux travaux pratiques de Biochimie et de Biologie moléculaire.
    [Show full text]
  • Dry Eye Disease: a Review of Epidemiology in Taiwan, and Its Clinical Treatment and Merits
    Journal of Clinical Medicine Review Dry Eye Disease: A Review of Epidemiology in Taiwan, and its Clinical Treatment and Merits 1, 2,3, 4,5 2,3 6 Yu-Kai Kuo y, I-Chan Lin y, Li-Nien Chien , Tzu-Yu Lin , Ying-Ting How , Ko-Hua Chen 3,7, Gregory J. Dusting 8,9 and Ching-Li Tseng 6,10,11,12,* 1 School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan 2 Department of Ophthalmology, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan 3 Department of Ophthalmology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan 4 School of Health Care Administration, College of Management, , Taipei Medical University, Taipei 11031, Taiwan 5 Health and Clinical Data Research Center, College of Public Health, Taipei Medical University, Taipei 11031, Taiwan 6 Graduate Institute of Biomedical Materials & Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei 11031, Taiwan 7 Department of Ophthalmology, Taipei Veterans General Hospital, Taipei 11217, Taiwan 8 Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC 3002, Australia 9 Ophthalmology, Department of Surgery, University of Melbourne, East Melbourne, VIC 3002, Australia 10 Institute of International PhD Program in Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei 11031, Taiwan 11 Research Center of Biomedical Device, College of Biomedical Engineering, Taipei Medical University, Taipei 11031, Taiwan 12 International PhD Program in Cell Therapy and Regenerative Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan * Correspondence: [email protected]; Tel.: +886-2736-1661 (ext.
    [Show full text]
  • TFOS DEWS II Clinical Trial Design Report
    The Ocular Surface 15 (2017) 629e649 Contents lists available at ScienceDirect The Ocular Surface journal homepage: www.theocularsurface.com TFOS DEWS II Clinical Trial Design Report * Gary D. Novack, PhD a, b, 1, , Penny Asbell, MD c, Stefano Barabino, MD, PhD d, Michael V.W. Bergamini, PhD e, f, Joseph B. Ciolino, MD g, Gary N. Foulks, MD h, Michael Goldstein, MD i, Michael A. Lemp, MD j, Stefan Schrader, MD, PhD k, Craig Woods, PhD, MCOptom l, Fiona Stapleton, PhD, MCOptom m a Pharma Logic Development, San Rafael, CA, USA b Departments of Pharmacology and Ophthalmology, University of California, Davis, School of Medicine, CA, USA c Department of Ophthalmology, Icahn School of Medicine at Mt Sinai, New York, NY, USA d Clinica Oculistica, University of Genoa, Italy e Nicox Ophthalmics, Inc., Fort Worth, TX, USA f University of North Texas Health Science Center, Fort Worth, TX, USA g Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA h Emeritus Professor of Ophthalmology, University of Louisville School of Medicine, Louisville, KY, USA i Department of Ophthalmology, New England Medical Center and Tufts University, Boston, MA, USA j Department of Ophthalmology, School of Medicine, Georgetown University, Washington, DC, USA k Department of Ophthalmology, Heinrich-Heine University, Düsseldorf, Germany l Deakin Optometry, School of Medicine, Deakin University, Geelong, Australia m School of Optometry and Vision Science, UNSW Australia, Sydney, NSW, Australia article info abstract Article history: The development of novel therapies for Dry Eye Disease (DED) is formidable, and relatively few treat- Received 5 May 2017 ments evaluated have been approved for marketing.
    [Show full text]
  • Inhibitors & Agonists Compound Screening Libraries
    www.MedChemExpress.com MedChemExpress Inhibitors & Agonists 25,000+ Specific Inhibitors & Agonists Targeting 20+ Classic Signaling Pathways Compound Screening Libraries 50+ Compound Screening Libraries Optimized for Disease Mechanism Revealing & Drug Repurposing Nature. 2020 Apr;580(7803):386-390. Cell. 2020 Apr 6. pii: S0092-8674(20)30268-3. Cell. 2020 Mar 5;180(5):941-955.e20. Nature. 2020 Mar;579(7799):433-437. Science. 2020 Feb 14;367(6479):806-810. Cell. 2020 Feb 20;180(4):645-654.e13. Nature. 2019 Dec;576(7786):274-280. Cell. 2019 Dec 12;179(7):1483-1498.e22. Cell. 2019 Dec 12;179(7):1566-1581.e16. Nature. 2019 Nov;575(7782):375-379. Nature. 2019 Nov;575(7784):683-687. Nature. 2019 Oct;574(7777):264-267. Cell. 2019 Oct 31;179(4):864-879.e19. Nat Nanotechnol. 2019 Oct;14(10):988-993. Publications Citing Use of MCE Products Citing Use of Publications Nat Biotechnol. 2019 Oct;37(10):1209-1216. Cell. 2019 Aug 22;178(5):1145-1158.e20. Cell. 2019 Aug 22;178(5):1132-1144.e10. Nature. 2019 Jul;571(7763):127-131. Science. 2019 Jul 19;365(6450). Cell. 2019 Jul 25;178(3):585-599.e15. Cell. 2019 Jul 11;178(2):330-345.e22. Inhibitors & Agonists “ 25,000+ selective Inhibitors and Agonists We offer Targeting 375 key proteins in 20+ signaling pathways only the Applications in different disease areas highest- Screening Libraries grade MCE Compound Screening Libraries consist of 10,000+ small molecules with products! validated biological and pharmacological activities Quality Our robust quality control methods assure product high quality and purity.
    [Show full text]