Properties of the human tear film lipid layer - Insight through molecular simulations

Jelena Telenius

Research output: ThesisDoctoral ThesisMonograph

Abstract

The outer layer of human tear film – the tear film lipid layer – covers the surface of the eye. This layer is the interface between the tear film and the air surrounding the eye. Abnormal composition of the tear film and its lipid layer may have quite severe consequences for health in terms of the so-called "dry eyes syndrome". People with dry eyes experience uncomfortable feelings, which bear a resemblance to having "sand in the eyes", and they have also excessive tear production and blurry vision. In addition to the abnormal lipid composition, also abnormal secretion of the tears themselves can lead to the development of dry eyes. Untreated dry eyes can lead to inflammation of the eye surface, and even scarring of the eye surface tissue. Dry eyes are treated with eye drops, which are selected to match the symptoms of the patient – some people need more lipids to the layer, while some others lack the aqueous tears. In this thesis, the tear film lipid layer was investigated by the means of molecular dynamics simulations. First, it was investigated how lipids in a native composition organize themselves to the interface between air and water. The systems considered were exposed to varying interfacial areas to see what happens to the interfacial region during the early phases of closing and opening the eyes. Second, consequences of abnormal lipid compositions typical to blepharitis patients were explored. Further, these considerations were complemented with simulations of lipid layers with quite diverse compositions to elucidate the roles of certain specific lipids in the function of tear film lipid layers. It was found that the lipids form a layer to the very interface of air and water. In the normal tear film composition, phospholipids formed the main body of the interfacial layer, while cholesteryl esters were observed to penetrate into it, promoting tighter packing of the interfacial layer. When the system was exposed to decreasing interfacial area to investigate what happens when eyes are being blinked, triglycerides helped the layer to stay intact even at very small interfacial areas. Meanwhile, with lipid layers characteristic to blepharitis patients, the ability to form a continuous lipid layer to the surface was impaired. Should the tear film lipid layer really be a monolayer-like also in reality, the results suggest that each lipid type in the layer has a specific role to maintain the function of the layer: phospholipids form the interface, cholesteryl esters make it stiffer, and triglycerides enable easier adjustment to changes in interfacial area. The results presented in the thesis pave the way for new avenues in clinical research of dry eyes, and aid the developing of more suitable eye drops for the treatment of dry eye patients.
Translated title of the contributionIhmisen kyynelnesteen rasvakalvon ominaisuuksista - Näkökulmia molekyylidynamiikka-simulaatioista
Original languageEnglish
QualificationDoctor's degree
Awarding Institution
  • Aalto University
Supervisors/Advisors
  • Nieminen, Risto, Supervisor
  • Vattulainen, Ilpo, Advisor, External person
Publisher
Print ISBNs978-952-60-5489-6
Electronic ISBNs978-952-60-5490-2
Publication statusPublished - 2013
MoE publication typeG4 Doctoral dissertation (monograph)

Keywords

  • monolayer
  • coarse grained
  • MARTINI
  • molecular dynamics simulation
  • MD
  • tear film lipid layer
  • TFLL
  • dry eye syndrome

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