Most cited article - PubMed ID 24651175
Organization of lipids in the tear film: a molecular-level view
The ocular surface is in constant interaction with the environment and with numerous pathogens. Therefore, complex mechanisms such as a stable tear film and local immune defense mechanisms are required to protect the eye. This study describes the detection, characterization, and putative role of surfactant protein G (SP-G/SFTA2) with respect to wound healing and surface activity. Bioinformatic, biochemical, and immunological methods were combined to elucidate the role of SP-G in tear film. The results show the presence of SP-G in ocular surface tissues and tear film (TF). Increased expression of SP-G was demonstrated in TF of patients with dry eye disease (DED). Addition of recombinant SP-G in combination with lipids led to an accelerated wound healing of human corneal cells as well as to a reduction of TF surface tension. Molecular modeling of TF suggest that SP-G may regulate tear film surface tension and improve its stability through specific interactions with lipids components of the tear film. In conclusion, SP-G is an ocular surface protein with putative wound healing properties that can also reduce the surface tension of the tear film.
- Keywords
- dry eye, ocular surface, surface tension, surfactant protein, tear film,
- MeSH
- Humans MeSH
- Lipids analysis MeSH
- Surface Tension MeSH
- Cornea metabolism MeSH
- Tears * metabolism MeSH
- Dry Eye Syndromes * metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Lipids MeSH
The tear film at the ocular surface is covered by a thin layer of lipids. This oily phase stabilizes the film by decreasing its surface tension and improving its viscoelastic properties. Clinically, destabilization and rupture of the tear film are related to dry eye disease and are accompanied by changes in the quality and quantity of tear film lipids. In dry eye, eye drops containing oil-in-water emulsions are used for the supplementation of lipids and surface-active components to the tear film. We explore in detail the biophysical aspects of interactions of specific surface-active compounds, cetalkonium chloride and poloxamer 188, which are present in oil-in-water emulsions, with tear lipids. The aim is to better understand the macroscopically observed eye drops-tear film interactions by rationalizing them at the molecular level. To this end, we employ a multi-scale approach combining experiments on human meibomian lipid extracts, measurements using synthetic lipid films, and in silico molecular dynamics simulations. By combining these methods, we demonstrate that the studied compounds specifically interact with the tear lipid film enhancing its structure, surfactant properties, and elasticity. The observed effects are cooperative and can be further modulated by material packing at the tear-air interface.
- Keywords
- Langmuir trough, dilatation rheology, fluorescence microscopy, meibum, molecular dynamics, tear film, tear film lipid layer,
- MeSH
- Microscopy, Fluorescence * methods MeSH
- Quaternary Ammonium Compounds chemistry MeSH
- Humans MeSH
- Lipids * chemistry MeSH
- Fatty Alcohols chemistry MeSH
- Meibomian Glands metabolism MeSH
- Poloxamer chemistry MeSH
- Molecular Dynamics Simulation * MeSH
- Tears * chemistry MeSH
- Models, Theoretical MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- cetalkonium chloride MeSH Browser
- Quaternary Ammonium Compounds MeSH
- Lipids * MeSH
- Fatty Alcohols MeSH
- Poloxamer MeSH
Dry eye disease (DED) is a complex multifactorial disease that affects an increasing number of patients worldwide. Close to 30% of the population has experienced dry eye (DE) symptoms and presented with some signs of the disease during their lifetime. The significant heterogeneity in the medical background of patients with DEs and in their sensitivity to symptoms renders a clear understanding of DED complicated. It has become evident over the past few years that DED results from an impairment of the ocular surface homeostasis. Hence, a holistic treatment approach that concomitantly addresses the different mechanisms that result in the destabilization of the tear film (TF) and the ocular surface would be appropriate. The goal of the present review is to compile the different types of scientific evidence (from in silico modeling to clinical trials) that help explain the mechanism of action of cationic emulsion (CE)-based eye drop technology for the treatment of both the signs and the symptoms of DED. These CE-based artificial tear (AT) eye drops designed to mimic, from a functional point of view, a healthy TF contribute to the restoration of a healthy ocular surface environment and TF that leads to a better management of DE patients. The CE-based AT eye drops help restore the ocular surface homeostasis in patients who have unstable TF or no tears.
- Keywords
- artificial tear, cationic emulsion, dry eye, polar lipid, tear film lipid layer,
- MeSH
- Adult MeSH
- Emulsions chemistry pharmacology MeSH
- Homeostasis MeSH
- Humans MeSH
- Ocular Physiological Phenomena drug effects MeSH
- Surface Properties drug effects MeSH
- Tears physiology MeSH
- Dry Eye Syndromes drug therapy MeSH
- Healthy Volunteers statistics & numerical data MeSH
- Lubricant Eye Drops administration & dosage chemistry therapeutic use MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Comparative Study MeSH
- Names of Substances
- Emulsions MeSH
- Lubricant Eye Drops MeSH