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I. A. Butovich; Biochemistry and Biophysics of Human and Animal Tear Film Lipid Layer: From Composition to Structure to Function. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4154.
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© ARVO (1962-2015); The Authors (2016-present)
Human tear film (hTF) is the front line of ocular defense against various damaging factors of the environment. Its deterioration upon, for example, the onset of dry eye, and the medical consequences of such an event are irrefutable. However, the biochemical, biophysical, and physiological mechanisms of the hTF deterioration are complex, and are still considered a work-in-progress. Here we summarize the known facts and hypotheses about hTF and its outermost part - TF lipid layer (hTFLL), and cross-check them against newly made experimental observations.
Meibum samples collected from humans and selected animal species were analyzed by using chromatographic (HPLC), mass-spectrometric (MS), and Langmuir trough (LT) techniques and were cross-analyzed and supplemented with published independent observations. Molecular modeling and quantum chemical computations were conducted to determine the structural features of these lipid molecules in order to explain their putative roles in the hTF.
A new group of lipids - very long chain (O-acyl)-omega-hydroxy fatty acids (OAHFA) - was identified in human meibum by HPLC and MS. The acyl components were mostly C16-C20 fatty acids, while the omega-hydroxy fatty acids were typically C26-C34. Similar lipids were detected in the meibum samples of other species, too. These anionogenic compounds are proposed to fulfill a dual purpose. First, they are related to other, even more complex groups of di- and tri-esters (Nicolaides and Santos, 1985), and could be either their precursors, or degradation products. Second, OAHFA are the only ionizable lipids found in meibum in the quantities sufficient to serve as a "polar lipid sublayer" whose function is to support and stabilize the much thicker "nonpolar lipid sublayer" of the hTFLL. As computational experiments showed, these compounds share a common property of being able to reversibly flex, bend and condense under pressure, which can explain the elasticity and non-collapsibility of meibum layers under quasi-physiological conditions used in our LT experiments. Other detected compounds were very long chain wax and cholesteryl esters, di- and tri-esters, and triacylglycerols. More rigid lipid molecules were found to have detrimental effects on the stability of meibomian layers.
Flexibility and amphiphilicity of the newly discovered and described very long chain lipid species appear to be contributing factors in formation and stabilization of hTFLL. An updated model of hTF is proposed to accommodate these new qualitative and quantitative findings.
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