Meibum Composition Research Articles

Pilot, Prospective, Randomized, Double-masked, Placebo-controlled Clinical Trial of an Omega-3 Supplement for Dry Eye

To investigate the potential effect of dietary supplementation with omega-3 fatty acid on lipid composition of meibum, aqueous tear evaporation, and tear volume in patients with dry eye. In a pilot, prospective, randomized, double-masked study, patients with dry eye received a daily dose of fish oil, containing 450 mg of eicosapentaenoic acid, 300 mg of docosahexaenoic acid, and 1000 mg of flaxseed oil (TheraTears Nutrition; Advanced Vision Research, Woburn, MA) for 90 days. There were 2 patient visits: baseline and final. At these visits, patients completed the ocular surface disease index to score subjective symptoms, and slit-lamp examinations, breakup time, corneal staining, Schirmer type I, fluorophotometry, evaporometry, and collection of meibomian gland secretion samples for lipid composition analysis were performed. A total of 36 patients with dry eye completed the study. At the end of the study, 70% of the patients became asymptomatic, whereas for the placebo group, 37% [corrected] of the symptomatic patients became asymptomatic. Schirmer testing and fluorophotometry suggested that the omega-3 supplement increased tear secretion. The lipid composition of the samples collected from the omega-3 group was found to be very similar to that from the placebo group. No trends between groups were seen for other objective parameters. Dietary supplementation with omega-3 fatty acids in dry eye showed no significant effect in meibum lipid composition or aqueous tear evaporation rate. On the other hand, the average tear production and tear volume was increased in the omega-3 group as indicated by both Schirmer testing and fluorophotometry.

Identification of phospholipids in human meibum by nano-electrospray ionisation tandem mass spectrometry

Meibum is believed to be the major source of tear film lipids, which are vital in the prevention of excess evaporation of the aqueous phase. The complete lipid composition of meibum has yet to be established. While earlier studies reported the presence of phospholipids in human meibum, recent mass spectrometric studies have not detected them. In this study we use electrospray ionisation tandem mass spectrometry to investigate the presence of phospholipids in meibum and provide comparison to the phospholipid profile of tears. Lipids were extracted from human meibum and tear samples using standard biphasic methods and analysed by nano-electrospray ionisation tandem mass spectrometry using targeted ion scans. A total of 35 choline-containing phospholipids were identified in meibum and the profile of these was similar to that observed in tears, suggesting tear lipids are derived from meibum. The results shown here highlight the need for a combination of optimised techniques to enable the identification of the large range of lipid classes in meibum.

Retinal very long-chain PUFAs: new insights from studies on ELOVL4 protein

Compared with other mammalian tissues, retina is highly enriched in PUFA. Long-chain PUFA (LC-PUFA; C18-C24) are essential FAs that are enriched in the retina and are necessary for maintenance of normal retinal development and function. The retina, brain, and sperm also contain very LC-PUFA (VLC-PUFA; >C24). Although VLC-PUFA were discovered more than two decades ago, very little is known about their biosynthesis and functional roles in the retina. This is due mainly to intrinsic difficulties associated with working on these unusually long polyunsaturated hydrocarbon chains and their existence in small amounts. Recent studies on the FA elongase elongation of very long chain fatty acids-4 (ELOVL4) protein, however, suggest that VLC-PUFA probably play some uniquely important roles in the retina as well as the other tissues. Mutations in the ELOVL4 gene are found in patients with autosomal dominant Stargardt disease. Here, we review the recent literature on VLC-PUFA with special emphasis on the elongases responsible for their synthesis. We focus on a novel elongase, ELOVL4, involved in the synthesis of VLC-PUFA, and the importance of these FAs in maintaining the structural and functional integrity of retinal photoreceptors.

Physical Changes in Human Meibum with Age as Measured by Infrared Spectroscopy

Both lipids and mucins contribute to the stability of the tear film and lipids may inhibit tears from evaporating. Younger people have lower lipid viscosity, higher lipid volume, and a lower rate of tear evaporation. Since age-related changes in human meibum composition and conformation have never been investigated, as a basis for the study of lipid-associated changes with meibomian gland dysfunction, we used the power of infrared spectroscopy to characterize hydrocarbon chain conformation and packing in meibum from humans without dry eye symptoms in relation to age and sex. Meibum from normal human donors ranging in age from 3 to 88 years was studied. Meibum phase transitions were quantified by fitting them to a 4-parameter 2-state sigmoidal equation. Human meibum order and phase transition temperatures decrease with age and this trend may be attributed to lipid compositional changes. If meibum has the same thermodynamic properties on the surface of the tears as it does on the lid margin, a decrease in lipid-lipid interaction strength with increasing age could decrease the stability of tears since lipid-lipid interactions on the tear surface must be broken for the tear film to break up. This study also serves as a foundation to examine meibum conformational differences in meibum from people with meibomian gland dysfunction.

Meibom-Drüsen

The oily secretion (meibum) of the Meibomian glands forms the superficial layer of the pre-ocular tear film and reduces evaporation of the aqueous phase. Meibum is a complex mixture of various lipids and minor protein components as well as other components of the secretory meibocytes, which form a clear liquid at body temperature. The exact composition and functions of meibum are still partly unknown, in particular the interaction of the water insoluble non-polar lipids with the polar, partly water soluble, lipids and potentially with proteins, which altogether interact to maintain the connection with the underlying aqueous tear phase. Meibum is transported within the gland by the force of secretory pressure from continuous secretion and by muscular action of the orbicularis muscle and Riolans muscles during blinking. After delivery of meibum onto the posterior lid margin the oil moves from the posterior lid margin reservoir onto the tear meniscus and is pulled as a thin layer onto the pre-ocular tear film every time the lid opens. During lid closure it is compressed and a small part is continuously renewed. Meibum also has a barrier function against the spillage of tears over the inner border of the lid and against the entry of skin lipids (sebum) from the free lid margin.

On the Lipid Composition of Human Meibum and Tears: Comparative Analysis of Nonpolar Lipids

To qualitatively compare the nonpolar lipids present in meibomian gland (MG) secretions (samples T1) with aqueous tears (AT) collected from the lower tear menisci of healthy, non-dry eye volunteers using either glass microcapillaries (samples T2) or Schirmer test strips (samples T3). Samples T1 to T3 were analyzed with the use of high-pressure liquid chromatography/positive ion mode atmospheric pressure chemical ionization mass spectrometry. Where possible, the unknown lipids were compared with known standards. Samples T1 had the simplest lipid composition among all the tested specimens. Samples T2 and T3 were similar to each other but were noticeably different from samples T1. In addition to all the compounds detected in samples T1, lower molecular weight wax esters and other compounds were found in samples T2 and T3. No appreciable amounts of fatty acid amides (e.g., oleamide), ceramides, or monoacyl glycerols were routinely detected. The occasionally observed minor signals of oleamide (m/z 282) in samples T3 were attributed to the contamination of the samples with common plasticizers routinely found in plastic ware extractives and organic solvents. The MG is a prominent source of lipids for the tear film. However, it would have been a mistake to exclude from consideration other likely sources of lipids such as conjunctiva, cornea, and tears produced by the lacrimal glands. These data showed that lipids in AT are more complex than MG secretions, which necessitates more cautious interpretation of the functions of the latter in the tear film.

Meibomianitis

To determine abnormal meibomian gland secretion polar lipids from meibomianitis patients and to determine the significance of these lipid differences. Meibomian gland secretions were collected from controls and patients with chronic blepharitis. These meibomian gland lipids (meibum) were first separated by thin-layer chromatography. Polar lipids were then separated utilizing high-pressure liquid chromatography with ultraviolet detection. Individual peaks were identified by comparison to standards and retention time. A polar lipid with an HPLC retention time longer than either phosphatidylcholine or sphingomyelin and shorter than phosphatidylethanolamine was significantly greater in the meibomianitis group (P<0.05) compared with other chronic blepharitis groups and normals. This polar lipid's retention time was similar to that of dimethylphosphatidylcholine or possibly lysophosphatidylcholine. Additionally, meibomianitis polar lipids' normal fatty acids were highly unsaturated and differed from those of other groups, none of which were unsaturated. Many of the most significant differences in meibomianitis meibum composition occur in the polar lipids rather than the nonpolar lipids. Further investigations will determine the true significance of these findings.

Meibomian gland and tear film lipids: structure, function and control.

Current understanding of the interactions between composition and function in the tear film is inadequate or misleading, especially as it pertains to the tear film lipid layer. This inadequacy begins as the primary source of the lipids, the meibomian gland orifice, releases its aliquot of meibum onto the aqueous-mucin layer. The polar and nonpolar lipid composition of meibum and the ionic composition of the aqueous-mucin layer result in formation of a functional tear film lipid monolayer. Many external parameters constrain lipid composition, including initial formation of a composite monolayer with polar and nonpolar phases, adequate fluidity near body temperature, ability to undergo compression and expansion without extensive hysteresis (as during a blink) and resistance to enzymatic degradation. Lipid type, as well as fatty acid and alcohol composition, affects each process.KeywordsHurdle RateOphthalmic DrugOphthalmic EmulsionEarly Stage TrialSuccessful Pharmacological TreatmentThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

MEIBOMIAN GLAND AND TEAR FILM LIPIDS: STRUCTURE, FUNCTION AND CONTROL.

Current understanding of the interactions between composition and function in the tear film is inadequate or misleading, especially as it pertains to the tear film lipid layer. This inadequacy begins as the primary source of the lipids, the meibomian gland orifice, releases its aliquot of meibum onto the aqueous-mucin layer. The polar and nonpolar lipid composition of meibum and the ionic composition of the aqueous-mucin layer result in formation of a functional tear film lipid monolayer. Many external parameters constrain lipid composition, including initial formation of a composite monolayer with polar and nonpolar phases, adequate fluidity near body temperature, ability to undergo compression and expansion without extensive hysteresis (as during a blink) and resistance to enzymatic degradation. Lipid type, as well as fatty acid and alcohol composition, affects each process.

Meibomian Gland Dysfunction and Tear Film Abnormalities in Rosacea

In order to determine the relationship between meibomian gland dysfunction and tear film abnormalities in rosacea, tear film flow and stability and meibomian gland function were assessed in 43 consecutive patients. Schirmer, tear film break-up time, and meibomian gland function values in patients with ocular rosacea (n = 28) were found to be significantly decreased as compared with those of the patients with only cutaneous involvement and control patients (p > 0.05). In patients with dermatologic rosacea (n = 15) these values were not different from those of the age- and sex-matched controls (p > 0.05). The effects of tetracycline and meibomian gland expression therapy also were investigated in patients with ocular rosacea. Neither meibomian gland expression therapy nor tetracycline administration had beneficial effects on decreased tear secretion, but tetracycline improved the break-up time values. Our findings showed a positive relationship between tear film abnormalities and meibomian gland dysfunction in patients with rosacea. Decreased tear secretion in patients with ocular rosacea would seem to be a result of structural changes secondary to meibomian gland dysfunction, and short break-up time might be due to an abnormal meibum composition.