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The Ocular Surface Jan 2022This study evaluated the presence and roles of cholesteryl esters (CEs) and wax esters (WEs) from human tear film and meibum in meibomian gland dysfunction (MGD).
PURPOSE
This study evaluated the presence and roles of cholesteryl esters (CEs) and wax esters (WEs) from human tear film and meibum in meibomian gland dysfunction (MGD).
METHODS
Out of 195 enrolled subjects, 164 and 179 subjects provided tear and meibum samples, respectively. Subjects were classified into normal, asymptomatic MGD, MGD, and mixed (MGD & aqueous deficient). The precorneal tear film (PCTF) thinning rate (evaporation) was measured using optical coherence tomography. Lipids extracted from tear and meibum samples were infused into a SCIEX 5600 TripleTOF mass spectrometer. CE and WE intensities quantified with Analyst 1.7 TF and LipidView 1.3 were compared across disease groups in MetaboAnalyst 5.0 and correlated with PCTF thinning rates.
RESULTS
The numbers of unique CEs and WEs identified in the samples were 125 and 86, respectively. Unsupervised Principal Component (PC) analysis and supervised Partial Least Square Discriminant analysis exhibited little separation among groups for both CEs and WEs in tears and meibum. Spearman's correlation analyses showed no association between either the first or second PC scores with PCTF thinning rates.
CONCLUSION
The abundances of human PCTF and meibum-derived CEs and WEs were independent of MGD disease status and PCTF thinning (evaporation). CEs and WEs alterations do not contribute to alterations in tear film dynamics in MGD, such as has been demonstrated by the (O-acyl) ω-hydroxy fatty acids (OAHFAs).
Topics: Esters; Fatty Acids; Humans; Meibomian Gland Dysfunction; Meibomian Glands; Tears
PubMed: 34774809
DOI: 10.1016/j.jtos.2021.10.009 -
Experimental Gerontology Jul 2012Dry eye disease is a prevalent eye disorder that in particular affects the elderly population. One of the major causes of dry eye, meibomian gland dysfunction (MGD),... (Review)
Review
Dry eye disease is a prevalent eye disorder that in particular affects the elderly population. One of the major causes of dry eye, meibomian gland dysfunction (MGD), shows increased prevalence with aging. MGD is caused by hyperkeratinization of the ductal epithelium of meibomian gland and reduced quantity and/or quality of meibum, the holocrine product that stabilizes and prevents the evaporation of the tear film. Of note, retinoids which are used in current anti-aging cosmetics may promote the development of MGD and dry eye disease. In this review, we will discuss the possible mechanisms of age-related MGD.
Topics: Aging; Animals; Disease Models, Animal; Dry Eye Syndromes; Humans; Meibomian Glands; Retinoids
PubMed: 22569356
DOI: 10.1016/j.exger.2012.03.020 -
International Journal of Molecular... Nov 2020Studies 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... (Review)
Review
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.
Topics: Animals; Disease Models, Animal; Dogs; Dry Eye Syndromes; Humans; Meibomian Gland Dysfunction; Meibomian Glands; Mice; Rabbits; Tears
PubMed: 33233466
DOI: 10.3390/ijms21228822 -
BMC Ophthalmology Apr 2023Orthokeratology lenses, which are worn overnight, are recommended for reducing myopia progression. They lie on the cornea and can influence the ocular surface by...
BACKGROUND
Orthokeratology lenses, which are worn overnight, are recommended for reducing myopia progression. They lie on the cornea and can influence the ocular surface by temporarily reshaping the corneal surface through a reverse geometry design. This study investigated the effect of overnight orthokeratology lenses on tear film stability and meibomian gland status in children aged 8-15 years.
METHODS
This prospective, self-controlled study included 33 children with monocular myopia who were prescribed orthokeratology lenses for at least one year. The experimental group (ortho-k group) comprised 33 myopic eyes. The control group comprised the emmetropic eyes of the same participants. Tear film stability and meibomian gland status were measured using a Keratograph 5M (Oculus, Wetzlar, Germany). Paired t-tests and Wilcoxon signed-rank tests were used to compare the data between the two groups.
RESULTS
At the one-year visit, the non-invasive first tear film break-up time (NIBUTf) values were 6.15 ± 2.56 s and 6.18 ± 2.61 s in the experimental and control groups, respectively. The lower tear meniscus height was 18.74 ± 0.05 μm and 18.65 ± 0.04 μm in these groups, respectively. No significant difference was observed in loss of meibomian glands or non-invasive average tear film break-up time between the experimental and control groups using Wilcoxon signed-rank tests.
CONCLUSIONS
The stability of the tear film and meibomian gland status were not significantly affected by wearing orthokeratology lenses overnight, indicating that continuous use of orthokeratology lenses for 12 months has a minimal effect on the ocular surface. This finding can help guide the clinical management of tear film quality with respect to the use of orthokeratology contact lenses.
Topics: Humans; Child; Prospective Studies; Meibomian Glands; Myopia; Cornea; Corneal Topography; Tears; Lacerations
PubMed: 37013481
DOI: 10.1186/s12886-023-02883-8 -
BMC Ophthalmology Dec 2015Meibomian gland dysfunction (MGD) is the major cause of evaporative dry eye disease (EDED) and dysfunction is widely thought to mechanistically involve ductal... (Review)
Review
Meibomian gland dysfunction (MGD) is the major cause of evaporative dry eye disease (EDED) and dysfunction is widely thought to mechanistically involve ductal hyperkeratinization, plugging and obstruction. This review re-evaluates the role of hyperkeratinization in MGD based on more recent findings from mouse models. In these studies, eyelids from normal young and old mice or mice exposed to desiccating stress were evaluated by immunofluorescent tomography and 3-dimensional reconstruction to evaluate gland volume, expression of hyperkeratinization markers and cell proliferation or stimulated Raman scattering (SRS) microscopy to assess lipid quality. Results indicate that aging mice show dropout of meibomian glands with loss of gland volume and a forward migration of the mucocutaneous junction anterior to the gland orifice; similar age-related changes that are detected in human subjects. Atrophic glands also showed evidence of epithelial plugging of the orifice without the presence of hyperkeratinization. Mice exposed to desiccating stress showed hyperproliferation of the meibomian gland and ductal dilation suggesting a marked increase in lipid synthesis. Lipid quality was also affected in EDED mice with an increase in the protein content of lipid within the duct of the gland. Overall, age-related changes in the mouse show similar structural and functional correlates with that observed in clinical MGD without evidence of hyperkeratinization suggesting that gland atrophy may be a major cause of EDED. The response of the meibomian gland to desiccating stress also suggest that environmental conditions may accelerate or potentiate age-related changes.
Topics: Animals; Atrophy; Dry Eye Syndromes; Eye Proteins; Eyelid Diseases; Humans; Keratins; Meibomian Glands; Mice
PubMed: 26817690
DOI: 10.1186/s12886-015-0132-x -
BMC Ophthalmology Jul 2020To observe the effects of chalazion and its treatments on meibomian gland function and morphology in the chalazion area. (Clinical Trial)
Clinical Trial Observational Study
BACKGROUND
To observe the effects of chalazion and its treatments on meibomian gland function and morphology in the chalazion area.
METHODS
This nonrandomized, prospective observational clinical study included 58 patients (67 eyelids) who were cured of chalazion, including 23 patients (23 eyelids) treated with a conservative method and 35 patients (44 eyelids) treated with surgery. Infrared meibomian gland photography combined with image analysis by ImageJ software was used to measure the chalazion area proportion. Slit-lamp microscopy was employed to evaluate meibomian gland function, and a confocal microscope was used to observe meibomian gland acinar morphology before treatment and 1 month after complete chalazion resolution.
RESULTS
At 1 month after chalazion resolution, the original chalazion area showed meibomian gland loss according to infrared meibomian gland photography in both groups. In patients who received conservative treatment, the meibomian gland function parameters before treatment were 0.74 ± 0.75, 0.48 ± 0.67, and 1.22 ± 0.60, respectively. One month after chalazion resolution, the parameters were 0.35 ± 0.49, 0.17 ± 0.49, and 0.91 ± 0.60, respectively; there was significant difference (P < 0.05). The proportion of the chalazion area before treatment was 14.90 (11.03, 25.3), and the proportion of meibomian gland loss at 1 month after chalazion resolution was 14.64 (10.33, 25.77); there was no significant difference (P > 0.05). In patients who underwent surgery, the meibomian gland function parameters before surgery were 0.93 ± 0.87, 1.07 ± 0.70, and 1.59 ± 0.76, respectively, and at 1 month after chalazion resolution, they were 0.93 ± 0.82, 0.95 ± 0.75, and 1.52 ± 0.70, respectively; there was no significant difference (P > 0.05). The proportion of the chalazion area before surgery was 14.90 (12.04, 21.6), and the proportion of meibomian gland loss at 1 month after chalazion resolution was 14.84 (11.31, 21.81); there was no significant difference (P > 0.05). The acinar structure could not be observed clearly in the meibomian gland loss area in most patients.
CONCLUSIONS
Chalazion causes meibomian gland loss, and the range of meibomian gland loss is not related to the treatment method but to the range of chalazion itself. A hot compress as part of conservative treatment can improve meibomian gland function at the site of chalazion in the short term.
Topics: Ascomycota; Chalazion; Eyelid Diseases; Humans; Meibomian Glands; Prospective Studies; Slit Lamp Microscopy; Tears
PubMed: 32652956
DOI: 10.1186/s12886-020-01557-z -
The Journal of Biological Chemistry Jun 2023Genes Sdr16c5 and Sdr16c6 encode proteins that belong to a superfamily of short-chain dehydrogenases/reductases (SDR16C5 and SDR16C6). Simultaneous inactivation of...
Genes Sdr16c5 and Sdr16c6 encode proteins that belong to a superfamily of short-chain dehydrogenases/reductases (SDR16C5 and SDR16C6). Simultaneous inactivation of these genes in double-KO (DKO) mice was previously shown to result in a marked enlargement of the mouse Meibomian glands (MGs) and sebaceous glands, respectively. However, the exact roles of SDRs in physiology and biochemistry of MGs and sebaceous glands have not been established yet. Therefore, we characterized, for the first time, meibum and sebum of Sdr16c5/Sdr16c6-null (DKO) mice using high-resolution MS and LC. In this study, we demonstrated that the mutation upregulated the overall production of MG secretions (also known as meibogenesis) and noticeably altered their lipidomic profile, but had a more subtle effect on sebogenesis. The major changes in meibum of DKO mice included abnormal accumulation of shorter chain, sebaceous-type cholesteryl esters and wax esters (WEs), and a marked increase in the biosynthesis of monounsaturated and diunsaturated Meibomian-type WEs. Importantly, the MGs of DKO mice maintained their ability to produce typical extremely long chain Meibomian-type lipids at seemingly normal levels. These observations indicated preferential activation of a previously dormant biosynthetic pathway that produce shorter chain, and more unsaturated, sebaceous-type WEs in the MGs of DKO mice, without altering the elongation patterns of their extremely long chain Meibomian-type counterparts. We conclude that the Sdr16c5/Sdr16c6 pair may control a point of bifurcation in one of the meibogenesis subpathways at which biosynthesis of lipids can be redirected toward either abnormal sebaceous-type lipidome or normal Meibomian-type lipidome in WT mice.
Topics: Animals; Mice; Cholesterol Esters; Lipid Metabolism; Mass Spectrometry; Meibomian Glands; Tears
PubMed: 37075844
DOI: 10.1016/j.jbc.2023.104725 -
International Journal of Molecular... Jul 2022Meibomian glands (MGs) and their holocrine secretion-meibum-play crucial roles in the physiology of the eye, providing protection from environmental factors and...
Meibomian glands (MGs) and their holocrine secretion-meibum-play crucial roles in the physiology of the eye, providing protection from environmental factors and desiccation, among other functions. Importantly, aging was implicated in the deterioration of the morphology and functions of MGs, and the quantity and quality of meibum they produce, leading to a loss of its protective properties, while the meibum of young individuals and experimental animals provide ample protection to the eye. Currently, the molecular mechanisms of meibum biosynthesis (termed meibogenesis) are not fully understood. To characterize the physiological changes in developing and maturing MGs, we studied the lipidomes and transcriptomes of mouse MGs ranging from newborns to adults. The results revealed a gradual increase in the critical genes of meibogenesis (such as , , , and , among others) that positively correlated with the biosynthesis of their respective lipid products. The MG transcriptomes of young and adult mice were also analyzed using single-cell RNA sequencing. These experiments revealed the existence of multiple unique populations of MG cells (meibocytes, epithelial cells, and others) with specific combinations of genes that encode meibogenesis-related proteins, and identified clusters and subclusters of cells that were tentatively classified as meibocytes at different stages of differentiation/maturation, or their progenitor cells. A hypothesis was formulated that these cells may produce different types of lipids, and contribute differentially to the Meibomian lipidome.
Topics: Acyltransferases; Animals; Lipidomics; Lipids; Meibomian Glands; Mice; Tears; Transcriptome
PubMed: 35887230
DOI: 10.3390/ijms23147884 -
Archives of Ophthalmology (Chicago,... Apr 2011To identify age-related changes in human meibomian glands that may be associated with meibomian gland dysfunction (MGD).
OBJECTIVE
To identify age-related changes in human meibomian glands that may be associated with meibomian gland dysfunction (MGD).
METHODS
Excess eyelid tissue from 36 patients (age range, 18-95 years, 19 female, 17 male) who underwent canthoplasty procedures were used. Dermatologic history, age, and presence of MGD were recorded. Samples were frozen, sectioned, and stained with specific antibodies against peroxisome proliferator-activated receptor γ (PPARγ) to identify meibocyte differentiation, Ki67 nuclear antigen to identify cycling cells, and CD45 to identify inflammatory cell infiltration.
RESULTS
Staining for PPARγ showed cytoplasmic and nuclear localization in the 2 youngest subjects (ages, 18 and 44 years). Older individuals (>60 years) showed predominantly nuclear staining, with cytoplasmic staining limited to the basal acinar cells in 17 of 31 subjects. The number of Ki67 positively stained basal cells were significantly elevated in the younger compared with older subjects based on linear regression analysis (r(2) = 0.35; P < .001). There was also a significant correlation between MG expression grade and CD45 cell infiltration (r = 0.414; P = .05).
CONCLUSIONS
These results indicate that aging human meibomian glands show decreased meibocyte differentiation and cell cycling that is associated with the development of MGD. Findings also suggest that altered PPARγ signaling may lead to acinar atrophy and development of an age-related hyposecretory MGD.
CLINICAL RELEVANCE
Meibomian gland dysfunction and evaporative dry eye are common age-related eyelid disorders. Understanding the underlying mechanism of MGD may lead to the development of novel therapeutic strategies to treat this disease.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aging; Cell Differentiation; Cell Proliferation; Eyelid Diseases; Female; Fluorescent Antibody Technique, Indirect; Humans; Ki-67 Antigen; Leukocyte Common Antigens; Male; Meibomian Glands; Middle Aged; PPAR gamma
PubMed: 21482872
DOI: 10.1001/archophthalmol.2011.69 -
The Ocular Surface Jan 2021While mouse models of dry eye disease (DED) have been developed, studies evaluating the role of the meibomian glands limited by the inability to temporally document...
PURPOSE
While mouse models of dry eye disease (DED) have been developed, studies evaluating the role of the meibomian glands limited by the inability to temporally document changes. In this report we describe the development of a novel mouse transillumination meibography device and assess the ability of this device to detect age-related changes in the meibomian glands of young and old mice.
METHODS
The mouse meibography device was comprised of a 3 mm wide right angle prism attached to broad spectrum light source by an optical fiber. Eyelids were then pulled over the prism using double tooth forceps and imaged using a stereomicroscope and low light level camera. Meibomian glands from four young and four old male, BALB/c mice were then imaged and analyzed using ImageJ.
RESULTS
In young mice, meibography documented the presence of 7-8 meibomian glands appearing as black and distinct eyelid structures with the length shorter in the lower eyelid compared to the upper eyelids. Eyelids of old mice showed apparent dropout of meibomian glands along with smaller and more irregularly shaped acini. The mean acini area of one meibomian gland was 0.088 ± 0.025 mm in young mice and 0.080 ± 0.020 mm in old mice (p = 0.564), but the Meibomian gland density was significantly lower in older mice (41.7 ± 6.4%, 27.3 ± 4.2%) (p = 0.021).
CONCLUSION
We have developed an in vivo meibography device that may prove useful in sequentially documenting changes during development of meibomian gland dysfunction and following treatment.
Topics: Animals; Eyelid Diseases; Male; Meibomian Glands; Mice; Mice, Inbred BALB C; Tears; Transillumination
PubMed: 33075493
DOI: 10.1016/j.jtos.2020.08.012