Human Meibum Cholesteryl and Wax Ester Variability With Age, Sex, and Meibomian Gland Dysfunction

Abstract

PURPOSE. Relationships between tear film lipid (TFL) layer composition, structure, and function could provide insight into the etiology of dry eye. The molar ratio of cholesteryl ester (CE)/wax ester (WE) was measured in meibum from normal donors (M n) and compared with meibum from donors with meibomian gland dysfunction (M MGD). METHODS. CE/WE was measured using nuclear magnetic resonance spectroscopy. RESULTS. CE/WE was distributed into two populations with 81% distributed near 0.55 and 19% near 0.3. CE/WE were higher in donors 13 to 19 years old compared with donors 1 to 12 years old and 20 to 88 years old. CE/WE for M MGD was 30% lower, 0.34 6 0.04, compared with M n , 0.49 6 0.04. There were no sex differences in CE/WE. There were no significant racial differences between the CE/WE ratios for Asians and Caucasians. The CE/WE ratio was higher for blacks and lower for Hispanics compared to Caucasians. Due to the small number sampled, confirmation of the later racial results is needed. The packing of CE and WE in the TFL layer was proposed. CONCLUSIONS. Although M MGD contains much less CE than M n , factors other than the CE content, such as the levels of saturation and/or proteins, may be responsible for the higher order of M MGD. In addition to saturation, CE could contribute to the increase in order of M n between 0 and 20 years of age. Observed changes in the meibum content of CE alone is not likely to influence tear film stability.

Comprehensive profiling of Asian and Caucasian meibomian gland secretions reveals similar lipidomic signatures regardless of ethnicity

“…These factors, if properly accounted for, bring the CE/WE ratio reported by Lam et al much closer to our earlier estimates than they appear without corrections for saturated WE, Chl, and Chl-OAHFA. Importantly, no gross difference in the CE/WE ratio between Asians and Caucasians was found in an independent study 23 , though the implemented technique—NMR—by its nature is not well-suited for identifying and quantifying any individual lipids in complex mixtures of homologous compounds (such as meibum), and could not differentiate between CE and Chl-OAHFA, WE and DiAD, etc., having most value as a supplementary technique once the chemical composition of samples have been established by other methods.…”

“…Meibum characteristics were reported to be dependent on age 17 and sex 18 , though in our recent studies with human subjects 19 , 20 and laboratory animals 21 no effects of gender on meibomian lipids were observed. Also, our initial report 22 , followed by another communication 23 , questioned the role of ethnicity in meibogenesis. Nevertheless, the role of race in physiology and biochemistry of normal and abnormal MG remains an understudied topic.…”

Dyslipidemia and Meibomian Gland Dysfunction: Utility of Lipidomics and Experimental Prospects with a Diet-Induced Obesity Mouse Model

“…Meibum cholesteryl esters are decreased whereas proteins are increased in MGD eyes, compared to normal [73]. The combination of lipid saturation and lipid–protein interaction is thought to make meibum less fluid (more viscous and more ordered), making it difficult for meibum to be delivered at the lid margin and further blocking the gland orifices [1,77]. The stasis of meibum can change the MG and ocular surface microbiome with a shift towards glands that produce lipases to degrade meibum and/or those that produce toxic mediators and some inflammation.…”

Meibum lipid hydrocarbon chain branching and rheology after hematopoietic stem cell transplantation

“…For tear lipids in general, cholesteryl ester content [ 33 , 34 ], polar lipids and tear proteins generally enhance spreading of lipids on the surface of the aqueous layer of the tear film [ 35 , 36 ]. Decreased levels of certain polar lipids reported with dry eye [ 37 , 38 ] calls for investigations into amount of polar lipids in M HSCT which might be lower and may provide further insight into the relationship between composition, structure and function of meibum from donors with HSCT.…”

“…Commercial software (GRAMS 386; Galactic Industries Corp., Salem, NH) was used for phasing, curve fitting and integrating. Hydrocarbon chain branching [ 22 ], saturation [ 23 ] and the molar ratio of cholesteryl ester to wax ester [ 24 ] were calculated from the 1 H NMR spectra as described previously.…”