July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Influence of nonpolar lipids chain length on the stability of Tear Film Lipid Layer: a molecular level view by employing in silico modeling
Author Affiliations & Notes
  • Lukasz Cwiklik
    Institute of Physical Chemistry, Czech Academy of Sciences, Prague, Czechia
  • Kamila Riedlova
    Institute of Physical Chemistry, Czech Academy of Sciences, Prague, Czechia
  • Agnieszka Olzynska
    Institute of Physical Chemistry, Czech Academy of Sciences, Prague, Czechia
  • Tereza Dolejsova
    Institute of Physical Chemistry, Czech Academy of Sciences, Prague, Czechia
    Department of Genetics and Microbiology, Faculty of Science, Charles University, Prague, Czechia
  • Philippe Daull
    Novagali Innovation Center, Santen SAS, Evry, France
  • Jean-Sebastien Garrigue
    Novagali Innovation Center, Santen SAS, Evry, France
  • Footnotes
    Commercial Relationships   Lukasz Cwiklik, Santen SAS (F); Kamila Riedlova, None; Agnieszka Olzynska, None; Tereza Dolejsova, None; Philippe Daull, Santen SAS (E); Jean-Sebastien Garrigue, Santen SAS (E)
  • Footnotes
    Support  Czech Science Foundation grant 18-26751S
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 4163. doi:
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      Lukasz Cwiklik, Kamila Riedlova, Agnieszka Olzynska, Tereza Dolejsova, Philippe Daull, Jean-Sebastien Garrigue; Influence of nonpolar lipids chain length on the stability of Tear Film Lipid Layer: a molecular level view by employing in silico modeling. Invest. Ophthalmol. Vis. Sci. 2019;60(9):4163.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Nonpolar lipids are the most abundant components of the Tear Film Lipid Layer – the outermost structure of the Tear Film. This complex mixture of various classes of molecules is secreted by Meibomian glands and spread onto the tear-air interface lowering interfacial surface tension and hindering tear evaporation. In TFLL, the nonpolar lipids are accompanied by much less abundant polar lipid species which are responsible for an efficient spreading and stabilization of TFLL at the aqueous tear subphase. As demonstrated by our earlier in silico molecular level models, nonpolar and polar lipids readily and specifically interact to form a stable lipid layer on the Tear Film. These interactions predominantly involve the aliphatic chains of both lipid classes and are modulated by the chain length of involved lipids. Notably, the lengths of tear film lipid tails vary. Furthermore, in some drug formulations, relatively short so-called medium-chain triglycerides are used. We hypothesize that alterations of nonpolar lipids chain length and their saturation change TFLL stability.

Methods : In silico molecular dynamics simulations employing TFLL model in contact with aqueous subphase were performed. The model included several types of polar and nonpolar lipids. Nonpolar lipids with reduced chain length and different tail saturation were introduced in the nonpolar sublayer of the film. Experiments involving analogous lipid films consisting of synthetic lipid species were performed using Langmuir trough coupled with a fluorescence microscope.

Results : Nonpolar lipids with the relatively long and unsaturated chains, corresponding to that found under typical physiological conditions, form a well-behaving film at the water-air interface. In particular, they are relatively well separated from the aqueous subphase by a sublayer of polar lipids. A reduction of the chain length and chain saturation leads to an enhanced penetration of the short-chain nonpolar lipids into the polar sublayer and modification of its properties. Corresponding alterations of the lipid film structure were also observed experimentally using synthetic lipid mixtures.

Conclusions : In silico molecular dynamics simulations of TFLL-mimicking models support the hypothesis that shortening and saturating of nonpolar lipids chains modifies structure and properties of Tear Film Lipid Layer.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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