Publications : 2016

Rodrigues AD, Eaton JS, Murphy CJ. 2016. Attributes of the tear film in species used in preclinical ocular toxicology investigations of dry eye disease (DED). Society of Toxicology, Abstract #1610.

Abstract

The precorneal tear film (PTF) is dynamic, has numerous constituents, contributes to the maintenance of ocular surface health, and is a barrier to infection. Insufficiency or imbalance can result in tear film instability and dry eye disease (DED). Animal models for toxicity testing are best chosen with understanding of the components of the PTF. Here, we re-view the published attributes of the tear film of the rabbit and dog and draw comparisons to reported values for humans. References were iden-tified using online publication databases including PubMed, Medline and Google Scholar as well as books and journals accessible through UC Davis Health Sciences Libraries. Over 100 reports were identified spanning from as early as 1954 to present-day. Normative values for the following parameters were identified: total tear film thickness, lipid layer thickness, tear volume, tear flow rate, tear break up time (TBUT), and Schirmer tear test I (STT I). Lipid layer & total tear film thickness are greater in rabbits (0.18µm & 10µm) than in humans (0.08µm & 4µm). For dogs, lipid layer thickness was reported but data was limited (0.1µm); total tear film thickness was not reported. Tear volume in rabbits is sim-ilar to that of humans (7-8µL), but data was not found in dogs. Reported values for TBUT in rabbits varied (20-55sec), with similar values reported for dogs (19sec) and humans (18sec). Values for tear production as re-flected by STT I results were lower in rabbits (8mm/min), and greater in dogs (21mm/min) than humans (19mm/ 5min). Tear flow rate var-ied between rabbits (2.5µL/min), dogs (11µL/min), and humans (1µL/min). Of the major differences between species, large thickness of lipid layer in rabbits, and high tear flow rate in dogs were the most dramatic. Normative values are important for choosing a relevant species for pre-clinical toxicology studies, and to enhance translatability of results. A knowledge gap exists regarding fundamental physiochemical attributes of the tear film of species commonly used in development of palliatives and therapeutics for DED.