Clinical signs of meibomian gland dysfunction (MGD) are associated with changes in meibum sphingolipid composition.
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ABSTRACT:
SUBMITTER: Paranjpe V
PROVIDER: S-EPMC6529255 | biostudies-literature | 2019 Apr
REPOSITORIES: biostudies-literature
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Clinical signs of meibomian gland dysfunction (MGD) are associated with changes in meibum sphingolipid composition.
Paranjpe Vikram V Tan Jeremy J Nguyen Jason J Lee John J Allegood Jeremy J Galor Anat A Mandal Nawajes N
The ocular surface 20181212 2
<h4>Purpose</h4>Sphingolipids (SPL) play roles in cell signaling, inflammation, and apoptosis. Changes in SPL composition have been reported in individuals with MGD, but associations between clinical signs of MGD and compositional changes in meibum SPLs have not been examined.<h4>Methods</h4>Forty-three individuals underwent a tear film assessment. Groups were split into those with good or poor quality meibum. Meibum was collected then analyzed with liquid chromatography-mass spectroscopy to qua ...[more]
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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.).
| S-EPMC3109056 | biostudies-literature
Project description:Meibomian gland dysfunction (MGD) leads to meibum stasis and pathogenic bacteria proliferation. We determined meibum microbiota via next-generation sequencing (NGS) and examined their association with tear cytokine levels in patients with MGD. This cross-sectional study included 44 moderate-severe patients with MGD and 44 healthy controls (HCs). All volunteers underwent assessment with the ocular surface disease index questionnaire, Schirmer without anesthesia, tear break-up time, Oxford grading of ocular surface staining, and lid and meibum features. Sample collection included tears for cytokine detection and meibum for 16S rRNA NGS. No significant differences were observed in the α-diversity of patients with MGD compared with that in HCs. However, Simpson's index showed significantly decreased α-diversity for severe MGD than for moderate MGD (p = 0.045). Principal coordinate analysis showed no significant differences in β-diversity in meibum samples from patients with MGD and HCs. Patients with MGD had significantly higher relative abundances of Bacteroides (8.54% vs. 6.00%, p = 0.015) and Novosphingobium (0.14% vs. 0.004%, p = 0.012) than the HCs. Significantly higher interleukin (IL)-17A was detected in the MGD group than in the HC group, particularly for severe MGD (p = 0.008). Although Bacteroides was more abundant in the MGD group than in the HC group, it was not positively correlated with IL-17A. The relationship between core meibum microbiota and tear cytokine levels remains unclear. However, increased Bacteroides and Novosphingobium abundance may be critical in MGD pathophysiology.
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Project description:PurposeThe molecular basis of the tear film and lipid layer alterations in meibomian gland dysfunction (MGD) is unknown. This study aimed to identify and compare (O-acyl)-omega-hydroxy fatty acids (OAHFAs) derived from human meibum and tears in MGD.MethodsOf 195 eligible subjects (18-84 years, 62.6% female), 183 and 174 provided samples for tears and meibum, respectively. Subjects were classified into four groups: Normal, Asymptomatic MGD, MGD, and Mixed. Samples from the right eye of each subject were infused into the SCIEX 5600 TripleTOF mass spectrometer in negative ion mode. Lipid intensities identified with Analyst1.7 TF and SCIEX LipidView1.3 were normalized by an internal standard and total ion current, then statistically compared in MetaboAnalyst 4.0.ResultsIn meibum and tears, 76 and 78 unique OAHFAs were identified, respectively. The five most frequent and abundant OAHFAs were 18:2/16:2, 18:1/32:1, 18:1/30:1, 18:2/32:1, and 18:1/34:1. Two OAHFAs, 18:2/20:2 and 18:2/20:1, were identified only in tears. Initial univariate analysis revealed three differently regulated OAHFAs in meibum and eight in tears. Partial Least Square Discriminant Analysis showed 18:1/32:1, 18:2/16:2, 18:1/34:1 and 18:0/32:1 in tears, and 18:2/16:2, 18:1/32:1 and 18:2/32:2 in meibum, had variable importance in projection scores >1.5 and contributed the most to the separation of groups. In both meibum and tears, all OAHFAS except 18:2/16:2 were reduced in MGD compared to the normal group.ConclusionMGD is accompanied by differential expression of specific OAHFAs in meibum and tears. These results suggest OAHFAs play a role in the altered biochemical profile of the tear film lipid layer in humans with MGD.
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Project description:Meibomian gland dysfunction (MGD) may be the leading cause of dry eye syndrome throughout the world. However, the precise mechanism(s) underlying the pathogenesis of this disease is unclear. This study was conducted to identify meibomian gland genes that may promote the development and/or progression of human MGD.Lid tissues were obtained from male and female MGD patients and age-matched controls after eyelid surgeries (e.g., to correct entropion or ectropion). Meibomian glands were isolated and processed for RNA extraction and the analysis of gene expression.The results show that MGD is associated with significant alterations in the expression of almost 400 genes in the human meibomian gland. The levels of 197 transcripts, including those encoding various small proline-rich proteins and S100 calcium-binding proteins, are significantly increased, whereas the expression of 194 genes, such as claudin 3 and cell adhesion molecule 1, is significantly decreased. These changes, which cannot be accounted for by sex differences, are accompanied by alterations in many gene ontologies (e.g., keratinization, cell cycle, and DNA repair). The findings also show that the human meibomian gland contains several highly expressed genes that are distinct from those in an adjacent tissue (i.e., conjunctival epithelium).The results demonstrate that MGD is accompanied by multiple changes in gene expression in the meibomian gland. The nature of these alterations, including the upregulation of genes encoding small proline-rich proteins and S100 calcium-binding proteins, suggest that keratinization plays an important role in the pathogenesis of MGD.
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Project description:BackgroundIn the present study, we evaluated the correlation between meibomian gland dropout and meibum quality in the same central 8 meibomian glands of the eyelid.MethodsNinety-nine eyes of 91 patients with dry eye were included in the study. Dropout of the 8 central meibomian glands of the eyelids was graded as 0, 1, 2, or 3, according to the dropout area. The meibum quality was graded as follows: grade 0, no secretion; 1, inspissated/toothpaste consistency; 2, cloudy liquid secretion; and 3, clear liquid secretion. For 68 eyes of 68 patients, correlation analysis between dropout and meibum quality was performed. To precisely analyze the direct correlation between meibomian gland dropout in meibography and meibum quality, we evaluated 31 eyes of 23 patients with focal dropout in meibography.ResultsThe median (interquartile range) meiboscore was 1.0 (2.0) in the upper eyelids and 0.0 (1.0) in the lower eyelids. The median (interquartile range) meibum quality grade was 3.0 (1.0) in the upper eyelids and 1.0 (1.0) in the lower eyelids. No significant correlation between the meiboscore and meibum quality grade was detected in the upper (p =0.746) or lower (p =0.551) eyelids. Analysis of the direct correlation between meibomian gland dropout in meibography and meibum quality in patients with focal dropout (loss of 1 or 2 adjacent meibomian glands), however, indicated that meibomian glands with dropout secreted little to no meibum.ConclusionsOverall analysis revealed no relationship between meibomian gland dropout and meibum quality, but more detailed investigation of each meibomian gland alone revealed that meibomian glands with dropout secrete little to no meibum.
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Project description:Thermal pulsation (LipiFlow) has been advocated for meibomian gland dysfunction (MGD) treatment and was found useful. We aimed to evaluate the efficacy and safety of thermal pulsation in Asian patients with different grades of meibomian gland loss.A hospital-based interventional study comparing thermal pulsation to warm compresses for MGD treatment. Fifty patients were recruited from the dry eye clinic of a Singapore tertiary eye hospital. The ocular surface and symptom were evaluated before treatment, and one and three months after treatment. Twenty-five patients underwent thermal pulsation (single session), whereas 25 patients underwent warm compresses (twice daily) for 3 months. Meibomian gland loss was graded using infrared meibography, whereas function was graded using the number of glands with liquid secretion.The mean age (SD) of participants was 56.4 (11.4) years in the warm compress group and 55.6 (12.7) years in the thermal pulsation group. Seventy-six percent of the participants were female. Irritation symptom significantly improved over 3 months in both groups (P<0.01), whereas tear breakup time (TBUT) was modestly improved at 1 month in only the thermal pulsation group (P=0.048), without significant difference between both groups over the 3 months (P=0.88). There was also no significant difference in irritation symptom, TBUT, Schirmer test, and gland secretion variables between patients with different grades of gland loss or function at follow-ups.A single session of thermal pulsation was similar in its efficacy and safety profile to 3 months of twice daily warm compresses in Asians. Treatment efficacy was not affected by pretreatment gland loss.
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Project description:The aim of this study was to use swept-source anterior segment optical coherence tomography (OCT) to explore imaging the meibomian gland openings and to identify their in vivo characteristics in patients with obstructive meibomian gland dysfunction (MGD) and healthy participants. We enrolled 49 patients with MGD and 54 health controls in this case-control study. Each participant underwent slit-lamp examination, meibography, and OCT scanning. Sixteen patients with MGD underwent a repeat OCT examination after eyelid massage. The outcome measures included determinations of meibomian gland openings (orifices and terminal ducts) from OCT images and comparisons of the meibomian openings between patients with MGD and normal controls before and after meibomian gland massage. Using the same OCT scanning model, the number of visible orifices of the meibomian glands was similar between eyes with MGD and normal eyes (9.2 ± 2.3 vs. 9.7 ± 2.4). The mean diameter of the terminal ducts in patients with MGD was larger (120.22 ± 27.92 µm vs. 100.96 ± 20.30 µm) than in the normal controls, and had a larger coefficient of variation. Significant differences were observed in the mean diameter of the terminal ducts of patients with MGD before and after meibum gland massage (133.73 ± 27.81 μm vs. 102.26 ± 24.30 μm, p < 0.001). Patients with MGD have more diversified orifices and larger meibomian gland terminal duct diameters than normal subjects. In addition, meibomian gland terminal duct diameters seem to decrease in patients with MGD after meibum gland massage.
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