Iowa State University Capstones, Theses and Graduate Theses and Dissertations Dissertations 2020 An eye on the dog as a translational model for ocular pharmacology Lionel Sebbag Iowa State University Follow this and additional works at: https://lib.dr.iastate.edu/etd Recommended Citation Sebbag, Lionel, "An eye on the dog as a translational model for ocular pharmacology" (2020). Graduate Theses and Dissertations. 18223. https://lib.dr.iastate.edu/etd/18223 This Dissertation is brought to you for free and open access by the Iowa State University Capstones, Theses and Dissertations at Iowa State University Digital Repository. It has been accepted for inclusion in Graduate Theses and Dissertations by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. An eye on the dog as a translational model for ocular pharmacology by Lionel Sebbag A dissertation submitted to the graduate faculty in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY Major: Biomedical Sciences (Pharmacology) Program of Study Committee: Jonathan P. Mochel, Major Professor Albert E. Jergens M. Heather West Greenlee Joshua R. Beck Ann M. Perera The student author, whose presentation of the scholarship herein was approved by the program of study committee, is solely responsible for the content of this dissertation. The Graduate College will ensure this dissertation is globally accessible and will not permit alterations after a degree is conferred. Iowa State University Ames, Iowa 2020 Copyright © Lionel Sebbag, 2020. All rights reserved. ii DEDICATION This dissertation is lovingly dedicated to my parents, Monique and Michel For their endless love, support, and encouragement Je vous aime très fort, Terbah!! iii TABLE OF CONTENTS Page ACKNOWLEDGMENTS ............................................................................................................ vii ABSTRACT ................................................................................................................................... ix CHAPTER 1. GENERAL INTRODUCTION ................................................................................1 References ................................................................................................................................. 2 CHAPTER 2. FLUOROPHOTOMETRIC ASSESSMENT OF TEAR VOLUME AND TURNOVER RATE IN HEALTHY DOGS AND CATS ..............................................................4 Abstract ...................................................................................................................................... 4 Introduction ............................................................................................................................... 5 Materials and Methods .............................................................................................................. 6 Animals ................................................................................................................................ 6 Fluorophotometry ................................................................................................................. 7 Data analysis......................................................................................................................... 8 Results ....................................................................................................................................... 9 Discussion ................................................................................................................................ 10 References ............................................................................................................................... 14 Tables and Figures ................................................................................................................... 18 CHAPTER 3. KINETICS OF FLUORESCEIN IN TEAR FILM AFTER EYE DROP INSTILLATION IN BEAGLE DOGS: DOES SIZE REALLY MATTER? ................................22 Abstract .................................................................................................................................... 22 Introduction ............................................................................................................................. 23 Materials and Methods ............................................................................................................ 25 Animals .............................................................................................................................. 25 Tear film fluorescein following instillation of 1 vs. 2 drops .............................................. 25 Volumetric capacity of the palpebral fissure ...................................................................... 26 Tear turnover rate at various instilled volumes .................................................................. 27 Data analysis....................................................................................................................... 27 Results ..................................................................................................................................... 29 Volumetric capacity of the canine palpebral fissure .......................................................... 29 Periocular spillage of instilled solution .............................................................................. 29 Tear turnover rate ............................................................................................................... 30 Tear film fluorescein concentrations following 1 vs. 2 drops ............................................ 31 Discussion ................................................................................................................................ 31 References ............................................................................................................................... 36 Tables and Figures ................................................................................................................... 41 iv CHAPTER 4. HISTAMINE-INDUCED CONJUNCTIVITIS AND BREAKDOWN OF BLOOD-TEAR BARRIER IN DOGS: A MODEL FOR OCULAR PHARMACOLOGY AND THERAPEUTICS ................................................................................................................46 Abstract .................................................................................................................................... 46 Introduction ............................................................................................................................. 47 Materials and Methods ............................................................................................................ 49 Experimentally Induced Conjunctivitis in Dogs ................................................................ 49 Naturally Acquired Conjunctivitis in Dogs ........................................................................ 52 Data Analysis ..................................................................................................................... 53 Results ..................................................................................................................................... 54 Experimentally Induced Conjunctivitis in Dogs ................................................................ 54 Naturally Acquired Conjunctivitis in Dogs ........................................................................ 57 Discussion ................................................................................................................................ 57 References ............................................................................................................................... 61 Tables and Figures ................................................................................................................... 65 CHAPTER 5. IMPACT OF ACUTE CONJUNCTIVITIS ON OCULAR SURFACE HOMEOSTASIS IN DOGS ..........................................................................................................74 Abstract .................................................................................................................................... 74 Introduction ............................................................................................................................. 75 Materials and Methods ............................................................................................................ 76 Animals .............................................................................................................................. 76 Procedures .......................................................................................................................... 76 Data analysis....................................................................................................................... 78 Results ..................................................................................................................................... 78 Discussion ................................................................................................................................ 79 References ............................................................................................................................... 83 Tables and Figures ................................................................................................................... 86