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Patients with Sjӧgren's syndrome (SS) have dry eye associated with meibomian gland dysfunction (MGD). The meibum from donors with dry eye due to MGD but without SS (M MGD ) presents with lower levels of cholesteryl ester, less straight chains, and more ordered hydrocarbon chains compared with meibum from donors without MGD (Mn). The aim of the current study was to compare the composition and hydrocarbon chain conformation of meibum from donors with Sjögren's syndrome (Mss) to Mn and M MGD . Meibum was expressed from patients with SS using an ILUX instrument (Alcon Inc., Fort Worth TX). All of the nine meibum donors with SS were female. Meibum composition was characterized using 1 H-NMR and meibum hydrocarbon chain conformation was measured using fourier transform infrared spectroscopy. Meibum from every donor with SS measured contained a significantly (P < 0.01) higher cholesteryl ester/wax ester ratio and more straight chains compared with donors without SS or dry eye. None of the nine phase transitional parameters were significantly different, P > 0.05, for Mss compared with Mn. Nor was the CH 3 /CH 2 band height ratio used to estimate the number of hydrocarbon CH 3 and CH 2 moieties different, P = 0.22, for Mss compared with Mn. In conclusion, the compositional differences between Mss compared with Mn did not result in differences in any of the nine meibum lipid phase transitional parameters measured. The compositional differences observed between Mss and Mn could be markers for or contribute to SS as the differences could lead to tear film lipid packing differences other than conformational differences., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Diabetes is a significant risk factor for meibomian gland dysfunction (MGD), but its mechanism is poorly understood. The main function of the meibomian glands (MGs) is to synthesize, store, and secrete lipids. In this study, we found that the amount of lipids in the meibomian acini in STZ-induced type 1 diabetic mice decreased, and the lipid droplets became larger and irregular. In all, 31 lipid subclasses were identified in the mouse MGs, which contained 1378 lipid species in total through lipidomics analysis based on LC-MS/MS. Diabetes caused a significant increase in the content of ceramides (Cer) in the MGs but a significant decrease in the ration of sphingomyelin to ceramides (SM/Cer). The quantity of meibocytes in diabetic mice was dramatically decreased, and the proliferation activity was alleviated, which may be associated with cell cycle arrest caused by diabetes-induced abnormal Cer metabolism in MGs. We found an increase in macrophage and neutrophils infiltration in the diabetic MGs, which may be related to the significant reduction of AcCa in diabetic MGs. Taken together, the results of the present study demonstrated that diabetes induced disruption of lipid homeostasis in MGs, which may mediate the decreased cell proliferation and increased inflammation caused by diabetes in MGs., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Conjunctival impression cytology samples from patients with meibomian gland dysfunction (MGD), dry eye (DE), and healthy subjects (CT) were collected for determination of the degree of squamous metaplasia (SM) by PAS-hematoxylin staining and for comparative proteomic analyses by 2D-DIGE. The protein spots with discriminant expression were identified by MALDI-TOF/TOF mass spectrometry. Three independent statistical studies were conducted: i). Analysis of differential protein expression between study groups: We observed increased expression of proteins S100A4, S100A8, retinal dehydrogenase-1, peroxiredoxin-1, annexin-A1, annexin-A2, α-enolase, and glutathione S-transferase-P in DE, whereas the highest expression of peroxiredoxin-6, actin cytoplasmic-1, peroxiredoxin-2, and heat shock protein HSP-90-α was observed in MGD; ii). Correlation between changes in the proteome profile and the grade of SM: The expression of 5 different cytokeratins (KRT1, KRT4, KRT8, KRT10, and KRT13) correlated with the degree of SM; iii). Proteome profile differences between pathological and CT groups: An overall proteome analysis revealed upregulation of 9 proteins in the pathological groups (Annexin-A1, α-enolase, Annexin-A2, S100A8, cytokeratin-1, Peroxiredoxin-2 and Leukocyte elastase inhibitor) and downregulation of 2 proteins (Galectin-3 and Lipocalin-1). In conclusion, a sensitive proteomic approach to study conjunctival tissue collected from minimally invasive impression cytology was implemented. Differential proteomics analyses showed that in comparison with the MGD, the DE patients presented higher overexpression of proteins related to antimicrobial defense, tissue-damage response, and regulation of body fluid secretions. Changes in MGD proteome were associated with oxidative stress and anti-apoptotic processes. We found a correlation between the grade of SM and expression of proteins associated with cytoskeleton and keratinization. The studied pathological groups shared elements related to the defense and inflammatory responses. Dot blot assays of proteins ANXA1, S100A8, and S100A4 validated the proteomic results obtained from 2D-DIGE experiments and confirmed the correlation between the expression of these proteins and the clinical parameters., (Copyright © 2017. Published by Elsevier Ltd.)

The meibomian gland is the major contributor to the tear film lipid layer. It is generally accepted that meibomian gland secretions, i.e, meibum, play a critical role in the homeostasis of the tear film. Lipid components of meibum and their structure, as well as functions were intensively studied. However, the proteins from meibum have not attracted enough attention. This review summarizes current knowledge about protein components of the meibum, particularly their function on tear film and ocular surface, and changes in the proteins during meibomian gland dysfunction (MGD)., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

To examine the relation between changes in the free fatty acid (FFA) composition of human meibum and both objective signs and subjective symptoms of meibomian gland dysfunction (MGD), we analyzed the FFA content of meibum collected from both MGD patients and control subjects. Thirty-eight patients with MGD (13 men and 25 women; mean age ± SD, 66.9 ± 15.0 years) were evaluated. Various objective signs and subjective symptoms of MGD were assessed. Meibum was analyzed by liquid chromatography-Fourier transform mass spectrometry, and the relation between the FFA composition of meibum and each objective sign and subjective symptom was examined by principal component analysis (PCA). No relation was apparent between the FFA composition of meibum and individual subjective symptoms or objective signs of MGD. However, a PCA score plot for meibum samples grouped on the basis of the severity of both telangiectasia and plugging of meibomian gland orifices revealed clear separation of mild and severe groups. This separation of the two groups was largely due to a significantly increased linoleic acid content in meibum of the severe group (3.56%, versus 0.70% of total FFAs in the mild group). The relative amount of linoleic acid in meibum was thus associated with the severity of telangiectasia and plugging of gland orifices in MGD, suggesting that this FFA might contribute to the pathogenesis of these signs., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Nutrition disorders and their correlates such as obesity are increasingly prevalent worldwide. A number of studies to date have suggested numerous potential associations between diet and tear film health; this paper will provide a summary of the available literature. The tear film is characterized through its protein and lipid content and through clinical measurements of characteristics such as osmolarity, volume and stability. Malnutrition, protein and vitamin-A deficiencies are extremely deleterious to tear film health and supplementation with oral vitamin A in this setting is of clear benefit. The relative impact of diet on tear film within what would be considered normal ranges of consumption is less clear. A number of population studies have suggested that hyperlipidemia and a diet low in omega-3 fatty acids are risks factor for dry eye disease. Numerous studies have investigated the effectiveness of oral supplementation with antioxidants, omega-3 (e.g. fish oil and linseed oil) and omega-6 (e.g. evening primrose oil) fatty acids in the last 10 years. Taken together, these suggest a small benefit of oral supplementation on tear film volume, stability and decreased ocular symptoms in patients previously diagnosed with diseases involving the ocular surface (e.g. Sjögren's syndrome, meibomian gland dysfunction, dry eye disease) and contact lens wearers suffering from dry eye. More research is required to determine the exact composition, dosage and indications for their use and to fully characterize how these nutraceuticals modulate the tear film., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Protein-meibum and terpenoids-meibum lipid interactions could be important in the etiology of meibomian gland dysfunction (MGD) and dry eye symptoms. In the current model studies, attenuated total reflectance (ATR) infrared (IR) spectroscopy was used to determine if the terpenoid β-carotene and the major proteins in tears and meibum affect the hydrocarbon chain conformation and carbonyl environment of wax, an abundant component of meibum. The main finding of these studies is that mucin binding to wax disordered slightly the conformation of the hydrocarbon chains of wax and caused the wax carbonyls to become hydrogen bonded or experience a more hydrophilic environment. Lysozyme and lactoglobulin, two proteins shown to bind to monolayers of meibum, did not have such an effect. Keratin and β-carotene did not affect the fluidity (viscosity) or environment of the carbonyl moieties of wax. Based on these results, tetraterpenoids are not likely to influence the structure of meibum in the meibomian glands. In addition, these findings suggest that it is unlikely that keratin blocks meibomian glands by causing the meibum to become more viscous. Among the tear fluid proteins studied, mucin is the most likely to influence the conformation and carbonyl environment of meibum at the tear film surface., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Changes in the phase transition temperatures and conformation of human meibum lipid with age and meibomian gland dysfunction have been quantified but with analysis of less than 1% of the infrared spectral range. The remaining 99% of the spectral range was analyzed with principal component analysis (PCA) and confirms our previous studies and reveal further insights into changes that occur in meibum with age and disease. Infrared spectra of meibum from 41 patients diagnosed with meibomian gland dysfunction (Md) and 32 normal donors (Mn) were measured. Principal component analysis (PCA) was used to quantify the variance among the spectra and meibum protein was quantified using the infrared carbonyl and amide I and II bands. A training set of spectra was used to discriminate between Mn and Md with an accuracy of 93%. This shows that certain spectral regions (eigenvectors) contain compositional and structural information about the changes that occur with the principal component (variable), meibomian gland dysfunction. The spectral features of the major eigenvector indicate that Md contains more protein and relatively less CH(3) and cis = CH band intensity compared to Mn. The amount of protein was confirmed from relative infrared band intensities. Our study supports the idea that compositional differences result in meibum that is less fluid and more viscous with meibomian gland dysfunction so that less lipid flows out of the meibomian gland orifice as observed clinically. This study also demonstrates the power of the combination of infrared spectroscopy and PCA as a diagnostic tool that discriminates between Mn and Md., (Published by Elsevier Ltd.)