Correlations between bulk and surface properties of meibomian lipids with alteration of wax-to-sterol esters content

Abstract

In a recent study (Ewurum et al., 2021), wax (WE) and sterol esters (CE) from human meibum secretions (MGS) were separated and reconstituted with controlled WE/CE ratios (0%, 20%, 30%, 40%, 50%, 75% and 100% CE weight fractions). It was found that the alterations in the CE content of WE/CE mixtures modified the hydrocarbon chain conformation and packing of the mixture. A major question that emerges is whether the spectroscopic packing parameters determined for bulk meibum translate to a change in the performance of meibomian layers at the air/water interface, as it is the surface film functionality that is crucial for the performance of MGS at the ocular surface. The study of human meibum films with Langmuir surface balance was performed to access the surface properties at blink-like deformations of the film area. Surface pressure (π)-area (A) isocycles and stress relaxations were used to assess the layer's reorganization during area cycling and dilatational elasticity, respectively. The morphology of the films was monitored by Brewster angle microscopy. It was found that the increased order and chain melting temperature of the bulk samples correlated with a raise in the maximum surface pressure attained at minimal surface area and in the transient dilatational modulus of the meibomian layers. Such correlations may allow for development of an improved understanding between the bulk and surface properties of human meibum and of other natural and synthetic tear lipid films.

Relationship Between Human Meibum Lipid Composition and the Severity of Meibomian Gland Dysfunction: A Spectroscopic Analysis

“…R CE/WE is a major compositional variant in meibum, and we have found that meibum R CE/WE levels are associated with dry eye in patients with Parkinson's disease, 49 MGD, 35 – 37 and Sjögren's syndrome, 50 as well as in patients who received local plaque brachytherapy for choroidal melanoma. 51 Furthermore, changes in R CE/WE were shown to influence the rheology of tear lipids on an aqueous surface in vitro, 34 increasing the probability that it contributes to, rather than is a consequence of, evaporative DED. However, the answer to the question of cause or effect is not as simple as “a loss of CE increases lipid order, resulting in a loss of tear film stability and DED.” Meibum R CE/WE levels are elevated, rather than decreased, in patients with Sjögren's syndrome and dry eye.…”

“…Increased order and chain melting temperature of the bulk samples correlated with increases in the maximum surface pressure attained at minimal surface area and the transient dilatational modulus of the meibum layer at an air/water interface in vitro. 34 Thus, changes in the spectroscopic packing parameters determined for bulk meibum translated to changes in the performance of the meibum layer at an air/water interface, and likely translate to changes in the surface film functionality of the TFLL. In future studies, it would be beneficial to separate meibum WE and CE and to measure WE and CE chain length, branching, and saturation using NMR spectroscopy, and then to compare the WE and CE hydrocarbon chain compositions to hydrocarbon chain order (conformation) using infrared spectroscopy, rheology, 53 and Langmuir trough technology.…”

“…18 , 33 The molar ratio of CE to WE (R CE/WE ) in meibum influences structural changes and the rheology of the surface film formed by meibum lipid (i.e., the maximum surface pressure attained at minimal surface area) and the transient dilatational modulus. 34 Importantly, NMR and infrared spectroscopic studies have shown that R CE/WE in meibum is approximately 0.49 in human control subjects but is decreased in patients with MGD. 35 – 37 …”