Sdr16c5 and Sdr16c6 control a dormant pathway at a bifurcation point between meibogenesis and sebogenesis.

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.

Meibomian gland development: Where, when and how?

The Meibomian gland (MG) is an indispensable adnexal structure of eye that produces meibum, an important defensive component for maintaining ocular homeostasis. Normal development and maintenance of the MGs is required for ocular health since atrophic MGs and disturbances in composition and/or secretion of meibum result in major ocular pathologies, collectively termed as Meibomian gland dysfunction (MGD). Currently available therapies for MGD merely provide symptomatic relief and do not treat the underlying deficiency of the MGs. Hence, a thorough understanding of the timeline of MG development, maturation and aging is required for regenerative purposes along with signaling molecules & pathways controlling proper differentiation of MG lineage in mammalian eye. Understanding the factors that contribute to the development of MGs, developmental abnormalities of MGs, and changes in the quality & quantity of meibum with developing phases of MGs are essential for developing potential treatments for MGD. In this review, we compiled a timeline of events and the factors involved in the structural and functional development of MGs and the associated developmental defects of MGs during development, maturation and aging.

Meibum Lipidomic Analysis in Evaporative Dry Eye Subjects.

Meibomian Glands (MG) are sebaceous glands responsible for the production of meibum, the main component of the Tear Film Lipid Layer (TFLL). The TFLL facilitates the spread of the tear film over the ocular surface, provides stability and reduces tear evaporation. Alterations in meibum composition lead to different ocular alterations like Meibomian Gland Dysfunction (MGD) and subsequent Evaporative Dry Eye (EDE). The aim of the present study was to investigate the composition and abundance of meibum lipids and their relationship with eyelid margin abnormalities, lipid layer patterns and MG status. The study utilizes a lipidomic approach to identify and quantify lipids in meibum samples using an Elute UHPLC system. This system considered all four dimensions (mass/charge, retention time, ion mobility and intensity) to provide the accurate identification of lipid species. Samples were categorized as healthy or low/no signs of alteration (group 1) or severe signs of alteration or EDE/MGD (group 2). The current investigation found differences in Variable Importance in Projection lipid abundance between both groups for the MGD signs studied. Changes in meibum composition occur and are related to higher scores in eyelid margin hyperaemia, eyelid margin irregularity, MG orifice plugging, MG loss and lipid layer pattern.

Comparative Characterization of Human Meibomian Glands, Free Sebaceous Glands, and Hair-Associated Sebaceous Glands Based on Biomarkers, Analysis of Secretion Composition, and Gland Morphology.

Meibomian gland dysfunction (MGD) is one of the main causes of dry eye disease. To better understand the physiological functions of human meibomian glands (MGs), the present study compared MGs with free sebaceous glands (SGs) and hair-associated SGs of humans using morphological, immunohistochemical, and liquid chromatography-mass spectrometry (LCMS)-based lipidomic approaches. Eyelids with MGs, nostrils, lips, and external auditory canals with free SGs, and scalp with hair-associated SGs of body donors were probed with antibodies against cytokeratins (CK) 1, 8, 10, and 14, stem cell markers keratin 15 and N-cadherin, cell-cell contact markers desmoglein 1 (Dsg1), desmocollin 3 (Dsc3), desmoplakin (Dp), plakoglobin (Pg), and E-cadherin, and the tight junction protein claudin 5. In addition, Oil Red O staining (ORO) was performed in cryosections. Secretions of MGs as well as of SGs of nostrils, external auditory canals, and scalps were collected from healthy volunteers, analyzed by LCMS, and the data were processed using various multivariate statistical analysis approaches. Serial sections of MGs, free SGs, and hair-associated SGs were 3D reconstructed and compared. CK1 was expressed differently in hair-associated SGs than in MGs and other free SGs. The expression levels of CK8, CK10, and CK14 in MGs were different from those in hair-associated SGs and other free SGs. KRT15 was expressed differently in hair-associated SGs, whereas N-cadherin was expressed equally in all types of glands. The cell-cell contact markers Dsg1, Dp, Dsc3, Pg, and E-cadherin revealed no differences. ORO staining showed that lipids in MGs were more highly dispersed and had larger lipid droplets than lipids in other free SGs. Hair-associated SGs had a smaller number of lipid droplets. LCMS revealed that the lipid composition of meibum was distinctively different from that of the sebum of the nostrils, external auditory canals, and scalp. The 3D reconstructions of the different glands revealed different morphologies of the SGs compared with MGs which are by far the largest type of glands. In humans, MGs differ in their morphology and secretory composition and show major differences from free and hair-associated SGs. The composition of meibum differs significantly from that of sebum from free SGs and from hair-associated SGs. Therefore, the MG can be considered as a highly specialized type of holocrine gland that exhibits all the histological characteristics of SGs, but is significantly different from them in terms of morphology and lipid composition.

Formation of fatty alcohols-components of meibum lipids-by the fatty acyl-CoA reductase FAR2 is essential for dry eye prevention.

Various lipids (mainly meibum lipids secreted by the meibomian glands) are present in the tear film lipid layer and play important roles in tear stability and the health of the cornea and conjunctiva. Many meibum lipids contain fatty alcohols (FAls) with chain lengths ≥C24, but the fatty acyl-CoA reductases (FARs) that produce them remain unclear. Here, using cell-based assays, we found that the two FAR isozymes (FAR1 and FAR2) show different substrate specificities: FAR1 and FAR2 are involved in the production of C16-C18 and ≥C20 FAls, respectively. Next, we generated Far2 knockout (KO) mice and examined their dry eye phenotype and meibum lipid composition. These mice showed a severe dry eye phenotype, characterized by plugged meibomian gland orifices, corneal damage, and tear film instability. The plugging was attributed to an increase in the melting point of the meibum lipids. Liquid chromatography coupled with tandem mass spectrometry revealed that FAl-containing meibum lipids (wax monoesters and types 1ω, 2α, and 2ω wax diesters) with a hydroxyl group at position 1 were almost completely absent in Far2 KO mice. The levels of di-unsaturated (O-acyl)-ω-hydroxy fatty acids were higher in Far2 KO mice than in wild type mice, but those of tri-unsaturated ones were comparable, suggesting the presence of two synthesis pathways for type 1ω wax diesters. These results indicate the importance of FAl-containing meibum lipids in the formation of a functional tear film lipid layer. In addition, our study provides clues to the molecular mechanism of the biosynthesis of meibum lipids.

Dysregulation of Lipid Metabolism in Aging Meibomian Glands and Its Molecular Markers.

The main function of exocrine Meibomian glands (MGs) is to produce a lipid-rich secretion called meibum which plays a critical role in maintaining the ocular surface homeostasis of humans and most mammals. The chemical composition of meibum, and its quantity produced by MGs, largely determine whether it can fulfill its role successfully. Aging was frequently associated with the onset of various MG-related pathologies. The goal of this study was to determine how aging affects the chemical composition and quantity of meibum in mice, and identify possible molecular markers of aging. Unbiased, untargeted and targeted lipidomic evaluation of mouse MG lipids was conducted using liquid chromatography-high-resolution mass spectrometry, and the results were analyzed using Principal Component, Orthogonal Projections to Latent Structures Discriminant, and Partial Least Square Discriminant Analyses. We found that aging leads to dysregulation of lipid metabolism in MGs, changing the ratios of major classes of MG lipids (such as wax esters, triacylglycerols, and phospholipids) in a progressive manner. Several lipid species that belong to these groups of MG lipids are proposed as clear markers of aging in a mouse model.

Mouse models in studies on the etiology of evaporative dry eye disease.

Evaporative dry eye disease (DED) is a common ocular condition impacting the quality of life of millions of patients worldwide. The etiology of evaporative DED is related to dysfunction of meibomian glands (MGs), resulting in suboptimal yield or lipid composition of secreted meibum. The clinical manifestation of evaporative DED involves mechanical obstruction of the MG orifice and decreased tear film stability that leads to chronic eye irritation, inflammation, and progressive damage to the cornea and surrounding tissue. Despite its high prevalence, evaporative DED remains an unmet medical need. The main obstacle in the development of effective therapeutic strategies against this disease is inadequate knowledge about the complex arrays of lipogenic reactions (meibogenesis) in the MGs and a lack of suitable animal models of the human condition. In this review, we discuss the recent advances in the creation of genetically modified mouse models that recapitulate the phenotype of evaporative DED as well as their impact on our understanding of lipid biosynthesis in MGs and therapeutic strategies targeting meibogenesis.

Physiological effects of inactivation and the roles of Elovl3/ELOVL3 in maintaining ocular homeostasis.

Recently, elongase of very long chain fatty acids-3 (ELOVL3) was demonstrated to play a pivotal role in physiology and biochemistry of the ocular surface by maintaining a proper balance in the lipid composition of meibum. The goal of this study was to further investigate the effects of ELOVL3 ablation in homozygous Elovl3-knockout mice (E3hom) in comparison with age and sex matched wild-type controls (E3wt). Slit lamp examination of the ocular surface of mice, and histological examination of their ocular tissues, highlighted a severe negative impact of Elovl3 inactivating mutation on the Meibomian glands (MG) and conjunctiva of mice. MG transcriptomes of the E3hom and E3wt mice were assessed and revealed a range of up- and downregulated genes related to lipid biosynthesis, inflammation, and stress response, compared with E3wt mice. Heat stage polarized light microscopy was used to assess melting characteristics of normal and abnormal meibum. The loss of Elovl3 led to a 8°C drop in the melting temperature of meibum in E3hom mice, and increased its fluidity. Also noted were the excessive accumulation of lipid material and tears around the eye and severe ocular inflammation, among other abnormalities.

Relationship between meibomian gland loss in infrared meibography and meibum quality in dry eye patients.

BACKGROUND: In the present study, we evaluated the correlation between meibomian gland dropout and meibum quality in the same central 8 meibomian glands of the eyelid. METHODS: Ninety-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. RESULTS: The 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. CONCLUSIONS: Overall 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.

Dynamic Changes in the Gene Expression Patterns and Lipid Profiles in the Developing and Maturing Meibomian Glands.

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 Elovl3, Elovl4, Awat2, and Soat1, 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.

Surface Chemistry Study of the Interactions of Sesame Oil with Meibomian Films.

A possible approach for the treatment of meibomian gland disease (MGD) can be the supplementation of meibomian gland secretion (MGS) with nonpolar lipids (NPL) rich plant oils. Sesame oil (SO), approximately equal in monounsaturated fat (oleic acid, 40% of total) and polyunsaturated fat (linoleic acid, 42% of total), has shown multiple health benefits due to its anti-inflammatory and antioxidant effects. Thus, the interactions between SO and MGS in surface layers deserve further study. Therefore, pseudobinary films were formed with controlled MGS/SO molar ratios (0%, 10%, 30%, 50%, and 100% SO) at the air/water surface of the Langmuir trough over phosphate buffered saline (pH 7.4) subphase. Surface pressure (π)-area (A) isotherms and Brewster angle microscopy observations showed nonideal interactions where SO aggregates with MGS and complements the NPL stratum of the meibomian layers. The analysis of stress relaxation transients with Kohlrausch-Williams-Watts equation revealed that the supplementation of fixed amount of MGS with excess lipids via SO altered the dilatational elasticity of the films as reflected by the increase of the exponent ß. Thus, SO with its unique combination of high oxidative stability and abundance of long polyunsaturated acyl chains might be a useful supplement to MGS layers.

[Modern possibilities of studying the composition of meibomian glands secretion]. / Sovremennye vozmozhnosti issledovaniya sostava sekreta meibomievykh zhelez.

As the main source of various lipids, the meibomian glands are involved in the formation of lipid layer of the tear film and the maintenance of homeostasis of the ocular surface. This process is directly dependent on the chemical composition and thickness of the lipid layer. In addition to lipid components, the meibum also contains various proteins that affect the properties of the tear film. The introduction of various modifications of mass spectrometry into clinical practice is a new diagnostic approach that allows obtaining information about the composition of meibomian glands secretion and tears.

Lipid conformational order and the etiology of cataract and dry eye.

Lens and tear film lipids are as unique as the systems they reside in. The major lipid of the human lens is dihydrosphingomylein, found in quantity only in the lens. The lens contains a cholesterol to phospholipid molar ratio as high as 10:1, more than anywhere else in the body. Lens lipids contribute to maintaining lens clarity, and alterations in lens lipid composition due to age are likely to contribute to cataract. Lens lipid composition reflects adaptations to the unique characteristics of the lens: no turnover of lens lipids or proteins; the lowest amount of oxygen of any tissue; and contains almost no intracellular organelles. The tear film lipid layer (TFLL) is also unique. The TFLL is a thin (100 nm) layer of lipid on the surface of tears covering the cornea that contributes to tear film stability. The major lipids of the TFLL are wax esters and cholesterol esters that are not found in the lens. The hydrocarbon chains associated with the esters are longer than those found anywhere else in the body (as long as 32 carbons), and many are branched. Changes in the composition and structure of the 30,000 different moieties of TFLL contribute to the instability of tears. The focus of the current review is how spectroscopy has been used to elucidate the relationships between lipid composition, conformational order and function, and the etiology of cataract and dry eye.

A spectroscopic approach to measuring meibum lipid composition and conformation in donors with SjÓ§gren's syndrome.

Patients with SjÓ§gren'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 (MMGD) 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 MMGD. 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 1H-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 CH3/CH2 band height ratio used to estimate the number of hydrocarbon CH3 and CH2 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.

Meibum lipid composition in type 2 diabetics with dry eye.

PURPOSE: The purpose of this investigation was to analyze and compare the composition of meibum between type 2 diabetics with dry eye disease (DED) and control subjects to better reveal the pathologic mechanisms of the meibomian gland degeneration (MGD) and DED in type 2 diabetes mellitus (T2DM). METHODS: 90 subjects were divided into the following 4 groups: DM-DED group: T2DM patients with DED (n = 30); DM control group: DM patients without DED (n = 18); DED group: DED patients without DM (n = 26); naive control group: normal subjects (n = 16). The lipid composition of meibum samples collected from these subjects was analyzed by high-pressure liquid chromatography-mass spectrometry (HPLC-MS) system. The content of lipid features from 12 major lipid classes was compared among the 4 groups. RESULTS: A significantly lower level of triacylglycerols (TG) and wax esters (WE) was found between DM-DED patients and normal controls (P < 0.01), whereas the level of Cholesteryl Ester (CE) in DM-DED patients increased compared with DED patients (P < 0.05). The level of (O-acyl)-omega-hydroxy fatty acids (OAHFA) in DM-DED patients was significantly lower than that in normal controls (P < 0.01). An opposite higher level of phospholipids (PLs) was observed in DM-DED patients than that in normal controls (P < 0.01). CONCLUSIONS: T2DM could influence the expression of meibum lipids to further aggravate DED and MGD. Lower expression of TG,WE and OAHFA, higher expression of CE and PLs were discovered in meibum lipids of T2DM-DED.

Interactions of Meibum and Tears with Mucomimetic Polymers: A Hint towards the Interplay between the Layers of the Tear Film.

Recent clinical findings suggest that mucomimetic polymers (MMP) can alter not only the texture of the aqueous tear but also the spreading and structure of the tear film (TF) lipid layer, thereby allowing for their synchronized performance in vivo. Thus, we aimed to evaluate in vitro (i) the capability of pharmaceutically applicable MMP to ensure the formation of post-evaporative ferning patterns (a characteristic feature of the "healthy" tear colloid) and (ii) the MMP interactions with human meibum films accessed in the course of blink-like deformations via Langmuir surface balance and Brewster angle microscopy (BAM). Four MMP were used- hyaluronic acid (HA), cross-linked hyaluronic acid (CHA), carboxymethyl cellulose (CMC) and gellan gum (GG)- at the concentrations of 0.0001%, 0.001%, 0.01%, 0.05% and 0.1%. Significant differences were observed in the MMP fern formation capability: CHA (≥0.001%) > HA (≥0.01%) = CMC (≥0.01%) > GG (≥0.05%). All MMP affected the spreading of meibum, with BAM micrographs revealing thickening of the films. CHA was particularly efficient, showing concentration-dependent enhancement of tear ferning and of meibomian layer structure, surfactant properties and viscoelasticity. Thus, endogenous and exogenous MMP may play key roles for the concerted action of the TF layers at the ocular surface, revealing novel routes for TF-oriented therapeutic applications.

[Modern approaches to the treatment of meibomian gland dysfunction]. / Sovremennye podkhody k lecheniyu disfunktsii meibomievykh zhelez.

The eyelids are a delicate and complex dynamic structure with primary function to protect the eye surface. The term «meibomian gland dysfunction¼ (MGD) first appeared in the mid-1980s. This lesion is known to result in a disturbance of the tear film, eye irritation symptoms, clinically significant inflammation and diseases of the eye surface. The progression of MGD leads to hyperosmolarity of the tear film, its instability, an increase in the bacterial load of the eyelid margin, blepharitis and generalized inflammation of the ocular surface. For patients who require surgical treatment, a healthy eyelid is very important. Despite postoperative functional recovery, most of these patients experience dry eye syndrome (DES), which can lead to symptoms of eye irritation and deterioration of visual acuity due to instability of the tear film. In the early stages of MGD, it is advisable to begin treatment with a conversation about correct frequent blinking, rest during visual activity, adequate water intake, and a specific diet. Later, patients are advised to use an ultrasonic air humidifier, warm dry compresses, practice proper eyelid hygiene and perform massages, apply preservative-free lubricants, azithromycin, omega-3 preparations, and undergo local anti-inflammatory therapy. In case of a tick-borne infestation, the International Expert Group recommends the use of scrubs with 50% tea tree oil for treating the eyelids. In order to achieve a long-term effect or permanent remission, it is necessary to practice daily eyelid hygiene with the help of gels, special napkins and shampoos over a long period of time. Correctly selected medical treatment in accordance with the stage of the disease supplemented with massages and warm dry compresses lead to a significant improvement in the quality of life of patients with MGD and DES. The simplicity of eyelid hygiene is currently ensured by the availability of tools specially designed for the safe treatment of its edges, which have a complex histological and anatomical structure.

Delineating a novel metabolic high triglycerides-low waxes syndrome that affects lipid homeostasis in meibomian and sebaceous glands.

Meibomian glands that are embedded in tarsal plates of human eyelids, and sebaceous glands found in the skin, including that of eyelids, are two related types of holocrine glands that produce lipid-rich secretions called meibum and sebum. Pervasive ocular disorders, such as Meibomian gland dysfunction and dry eye, have been linked to changes in the lipid composition of meibum. However, in most described cases the changes were either small, or random, or insufficiently characterized on the molecular level. Here, we present results of comprehensive lipidomic analyses of meibum, tears and sebum of a patient whose secretions were highly abnormal (abnormal meibum, tears and sebum, or AMTS, patient). The lipidomes were characterized on the level of individual lipid species using ultra-high performance liquid chromatography and high resolution mass spectrometry. The major differences between the AMTS patient and normal age- and gender-matched subjects included, among others, severely diminished pools of normal meibomian lipids such as wax esters and cholesteryl esters in meibum and tears, a 2x increase in total cholesteryl esters to wax esters ratio, their skewed molecular profiles, a ~3x increase in free cholesterol to cholesteryl esters ratio, and, most importantly, a 20x to 30x increase in the triglicerides fraction over the norm. Sebum of the AMTS patient was also highly abnormal lacking major wax esters. Notably, the routine blood lipid panel test of the AMTS patient showed no abnormalities. The data imply that the AMTS patient had a severe, previously unreported, metabolic disorder that affected meibogenesis in Meibomian glands and sebogenesis in sebaceous glands. This is, to the best of our knowledge, a first observation of the condition that we have termed High Triglycerides/Low Waxes (HTLW) syndrome.

On the pivotal role of Elovl3/ELOVL3 in meibogenesis and ocular physiology of mice.

The purpose of this study was to examine the role of Elovl3 gene in meibogenesis and the impact of ELOVL3 protein ablation on the physiology of the mouse ocular surface and Meibomian glands (MGs). Elovl3 knockout, ELOVL3-ablated (E3hom) mice and their wild type littermates (E3wt) were studied side by side. E3hom mice had abnormal ocular phenotypes such as delayed eye opening, weeping eyes, crusty eyelids, eyelid edema, highly vascularized cornea and tarsal plates (TPs), slit eye, and increased tearing that resemble symptoms observed in human subjects with various forms of dry eye, MG dysfunction and blepharitis. Lipid profiling of E3hom TPs was conducted using chromatography and mass spectrometry. The analyses revealed that the lipid composition of E3hom TPs was strikingly different from that of their E3wt littermates. The mutation affected major classes of meibomian lipids - cholesteryl esters, wax esters, and cholesteryl esters of (O)-acylated w-hydroxy fatty acids. The studies illuminated the central role of ELOVL3 in producing C21:0-C29:0 fatty acids, including odd-chain and branched ones. Ablation of ELOVL3 leads to selective changes in the lipid composition of meibum, making E3hom mice instrumental in studying the mechanisms of the biosynthesis of meibum and modeling various pathologies of human ocular surface and adnexa.-Butovich, I. A., Wilkerson, A., Bhat, N., McMahon, A., Yuksel, S. On the pivotal role of Elovl3/ELOVL3 in meibogenesis and ocular physiology of mice.

Use of Intense Pulsed Light to Mitigate Meibomian Gland Dysfunction for Dry Eye Disease.

Dry Eye Disease (DED) is a common ocular condition that needs prompt diagnosis and careful treatment interventions. If left untreated, it can lead to numerous sight-threatening complications, including ulceration of the cornea, blepharitis, alterations of the tear film, conjunctivitis, and in severe cases, may lead to scarring, thinning, and even perforation of the cornea. Intense pulsed light (IPL) is a non-laser high-intensity light source that has shown to play a valuable role in dry eye disease. Recent evidence from various research works has shown that IPL modifies the mechanism of meibomian gland dysfunction (MGD), which helps to relieve the symptoms of DED. In this review, we demonstrated the mechanism of action of IPL, including its benefits on DED. The emerging evidence shows that the role of IPL in DED is novel and therapeutic. These results direct us to conclude that IPL is a potentially beneficial tool and essential future therapy for dry eye disease. Advances in the treatment of DED will lead to a better quality of life. However, tools to recognize potentially severe side effects of DED earlier in order to treat or prevent them must be developed.