Dataset Information

Meibomian Gland Dysfunction: What Have Animal Models Taught Us?

ABSTRACT: Studies have estimated that currently 344 million people worldwide and 16.4 million adults in the US have some form of dry eye disease (DED). It is believed that approximately 70% of DED cases are due to some form of evaporative dry eye, for which Meibomian gland dysfunction (MGD) is the major cause. Unfortunately, currently there is no effective treatment for MGD, and solely palliative care is available. Given the importance of MGD in DED, there has been a growing interest in studying Meibomian gland development, homeostasis and pathology, and, also, in developing therapies for treating and/or preventing MGD. For such, animal models have shown to be a vital tool. Much of what is known today about the Meibomian gland and MGD was learnt from these important animal models. In particular, canine and rabbit models have been essential for studying the physiopathology and progression of DED, and the mouse model, which includes different knockout strains, has enabled the identification of specific pathways potentially involved in MGD. Herein, we provide a bibliographic review on the various animal models that have been used to study Meibomian gland development, Meibomian gland homeostasis and MGD, primarily focusing on publications between 2000 and 2020.

SUBMITTER: Sun M

PROVIDER: S-EPMC7700490 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Meibomian Gland Dysfunction: What Have Animal Models Taught Us?

Sun Mingxia M Moreno Isabel Y IY Dang Michelle M Coulson-Thomas Vivien J VJ

International journal of molecular sciences 20201121 22

Studies have estimated that currently 344 million people worldwide and 16.4 million adults in the US have some form of dry eye disease (DED). It is believed that approximately 70% of DED cases are due to some form of evaporative dry eye, for which Meibomian gland dysfunction (MGD) is the major cause. Unfortunately, currently there is no effective treatment for MGD, and solely palliative care is available. Given the importance of MGD in DED, there has been a growing interest in studying Meibomian ...[more]

PMID: 33233466

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Project description:PurposeTo investigate the comparative efficacy of intense pulsed light (IPL) therapy alone with that of IPL plus meibomian gland expression (MGX) for meibomian gland dysfunction (MGD).MethodsThis is a prospective randomized crossover clinical trial. Sixty patients were enrolled and randomly assigned to two groups. All of patients underwent four treatment sessions in total, which were two weeks apart. Group 1 underwent two sessions of IPL therapy with MGX, as well as two sessions of IPL alone. Group 2 received two sessions of IPL therapy alone, and two sessions of IPL therapy with MGX. The following parameters were measured at baseline (BL), 2 weeks after the second treatment session (FU1), and 2 weeks after the fourth treatment session (FU2): tearfilm break-up time (BUT), Oxford grade for corneal staining, meibomian gland expressibility (MGE), meibum quality (MQ), and ocular surface disease index (OSDI). The separate effect of MGX on improvement of MGD parameters was evaluated using generalized estimating equation (GEE).ResultsThe mean age of the participants was 57.52 ± 10.50 years. The BUT, Oxford grade, MGE, MQ, and OSDI of both groups improved significantly (from baseline) by the end of four treatment sessions (FU2 compared to BL; all p-values <0.05). The MGE and MQ significantly improved after the first and second treatment sessions (FU1 compare to BL; all p-values < 0.001). However, the improvement was not statistically significant after the third and fourth treatment sessions (FU2 compared to FU1; p-value of 0.388 for MGE and 0.645 for MQ in group 1, 0.333 for MGE and 0.333 for MQ in group 2). The IPL plus MGX therapy produced greater improvements in the BUT scores than did IPL therapy alone (p = 0.003 by GEE). In contrast, the Oxford grade, MGE, MQ, and OSDI were not influenced by the addition of MGX to IPL (p = 0.642, 0.663, 0.731, and 0.840, respectively by GEE).ConclusionIPL therapy effectively improves the subjective symptoms and objective ocular findings of MGD. MGX enhanced the improvement of BUT driven by IPL therapy. The meibomian gland function (MGE and MQ) recovers faster in response to IPL therapy than did the other parameters.

Project description:Instability of the tear film with rapid tear break-up time is a common feature of aqueous-deficient and evaporative dry eye diseases, suggesting that there may be a shared structural abnormality of the tear film that is responsible for the instability. It may be that a change in the normal meibum lipid composition and conformation causes this abnormality. Principle component analyses of infrared spectra of human meibum indicate that human meibum collected from normal donors (Mn) is less ordered than meibum from donors with meibomian gland dysfunction (Md). In this study the conformation of Md was quantified to test this finding.Changes in lipid conformation with temperature were measured by infrared spectroscopy. There were two phases to our study. In phase 1, the phase transitions of human samples, Mn and Md, were measured. In phase 2, the phase transitions of model lipid standards composed of different waxes and cholesterol esters were measured.The phase-transition temperature was significantly higher (4°C) for the Md compared with the Mn of age-matched donors with no history of dry-eye symptoms. Most (82%) of the phase-transition temperatures measured for Md were above the values for Mn. The small change in the transition temperature was amplified in the average lipid order (stiffness) at 33.4°C. The average lipid order at 33.4°C for Md was significantly higher (30%, P = 0.004) than for Mn. The strength of lipid-lipid interactions was 72% higher for Md than for Mn. The ability of one lipid to influence the melting of adjacent lipids is termed cooperativity. There were no significant differences between Mn and Md in phase-transition cooperativity, nor was there a difference between Mn and Md in the minimum order or maximum order that Mn and Md achieved at very low and very high temperatures, respectively. The model wax studies showed that the phase transition of complex mixtures of natural lipids was set by the level of unsaturation. A double bond decreased the phase-transition temperature by approximately 40°C. The addition of a second CH CH moiety decreased the phase-transition temperature by approximately 19°C. Unsaturated waxes were miscible with saturated waxes. When a saturated wax was mixed with an unsaturated one, the saturated wax disproportionately increased the phase transition of the mixture by approximately 30°C compared with the saturated wax alone. Cholesterol ester had little effect on the phase-transition temperature of the waxes. Model studies indicated that changes in the amount of lipid saturation, rather than the amount of cholesterol esters, could be a factor in the observed conformational changes.Meibum lipid compositional changes with meibomian gland dysfunction reflect changes in hydrocarbon chain conformation and lipid-lipid interaction strength. Spectroscopic techniques are useful in studying the lipid-lipid interactions and conformation of lipid from individual patients. (ClinicalTrials.gov number, NCT00803452.).

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Meibomian Gland Dysfunction: What Have Animal Models Taught Us?

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Meibomian Gland Dysfunction: What Have Animal Models Taught Us?

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