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Computational and Structural... 2023Meibomian gland dysfunction (MGD) is a prevalent inflammatory disorder of the ocular surface that significantly impacts patients' vision and quality of life. The...
Meibomian gland dysfunction (MGD) is a prevalent inflammatory disorder of the ocular surface that significantly impacts patients' vision and quality of life. The underlying mechanism of aging and MGD remains largely uncharacterized. The aim of this work is to investigate lipid metabolic alterations in age-related MGD (ARMGD) through integrated proteomics, lipidomics and machine learning (ML) approach. For this purpose, we collected samples of female mouse meibomian glands (MGs) dissected from eyelids at age two months (n = 9) and two years (n = 9) for proteomic and lipidomic profilings using the liquid chromatography with tandem mass spectrometry (LC-MS/MS) method. To further identify ARMGD-related lipid biomarkers, ML model was established using the least absolute shrinkage and selection operator (LASSO) algorithm. For proteomic profiling, 375 differentially expressed proteins were detected. Functional analyses indicated the leading role of cholesterol biosynthesis in the aging process of MGs. Several proteins were proposed as potential biomarkers, including lanosterol synthase (Lss), 24-dehydrocholesterol reductase (Dhcr24), and farnesyl diphosphate farnesyl transferase 1 (Fdft1). Concomitantly, lipidomic analysis unveiled 47 lipid species that were differentially expressed and clustered into four classes. The most notable age-related alterations involved a decline in cholesteryl esters (ChE) levels and an increase in triradylglycerols (TG) levels, accompanied by significant differences in their lipid unsaturation patterns. Through ML construction, it was confirmed that ChE(26:0), ChE(26:1), and ChE(30:1) represent the most promising diagnostic molecules. The present study identified essential proteins, lipids, and signaling pathways in age-related MGD (ARMGD), providing a reference landscape to facilitate novel strategies for the disease transformation.
PubMed: 37675286
DOI: 10.1016/j.csbj.2023.08.026 -
Acta Ophthalmologica Jun 2024Dry eye disease is a highly prevalent condition, which can substantially impair quality of life, work productivity, and vision. It is considered an inflammatory disease... (Review)
Review
Dry eye disease is a highly prevalent condition, which can substantially impair quality of life, work productivity, and vision. It is considered an inflammatory disease and the most common cause is meibomian gland dysfunction. Despite many treatment alternatives being available, including artificial tears, warm compresses, antibiotics, and anti-inflammatory therapy, lasting treatment effects are rare. Over the last two decades, intense pulsed light therapy, after being well established in dermatology, has been gradually introduced to the field of ophthalmology to treat meibomian gland dysfunction. The purpose of the current article is to critically review the clinical studies assessing the use of intense pulsed light to treat meibomian gland dysfunction published to date. The vast majority of the included studies demonstrated improved symptoms and signs, although the degree of efficacy and its duration varied greatly depending on concomitant treatment, number of treatment sessions, and other factors. Several possible mechanisms of action concerning disease propagation and treatment efficacy are discussed. There is still a need for larger, randomised, longitudinal studies to define the most efficacious treatment regime and to predict which patients may benefit the most. More studies are needed on implementing biochemical analyses and machine learning algorithms. Such studies may prove beneficial in predicting treatment effects, defining optimal treatment regimens, and furthering our understanding of the mechanisms of action.
Topics: Humans; Meibomian Gland Dysfunction; Intense Pulsed Light Therapy; Meibomian Glands; Dry Eye Syndromes; Quality of Life; Tears
PubMed: 37702308
DOI: 10.1111/aos.15759 -
International Journal of Ophthalmology 2023To report ocular changes in rabbits after the implementation of three different induction methods to create dry eye (DE) conditions and provides evidence of DE-related...
AIM
To report ocular changes in rabbits after the implementation of three different induction methods to create dry eye (DE) conditions and provides evidence of DE-related disease evolution.
METHODS
Experimental methods were divided into 3 models. The first model used involved triple injection of complete Freund's adjuvant, 50 µL each, also called the meibomian gland dysfunction (MGD) model. In the second model, DE conditions were created by the resection of nictitating membranes (NM), Harderian glands (HG), and main lacrimal glands (LG), also called the LGR model. The third model involved the topical administration of benzalkonium chloride (BAK) 0.1% solution. The Schirmer test, ocular surface staining with fluorescein, and tear break-up time tests were implemented before and after excision. After euthanasia, the ocular tissues were dissected. Cornea, conjunctiva, and meibomian glands were treated with periodic acid-Schiff (PAS) staining and haematoxylin-eosin staining.
RESULTS
The MGD model triggered inflammation of meibomian glands. It detected changes in the lipid layer of the tear film. The bilateral resection of NM, HG, and LG reduced the watering layer of the tear film. The topical administration of BAK of 0.1% solution impacted the mucosal layer of the tear film.
CONCLUSION
Different changes are observed with different DE syndrome models. The composition of the tear film differ depending on which part of the eye is targeted. More studies need to be done to confirm whether an increased thickness of the cornea has any impact on the DE disease.
PubMed: 37602345
DOI: 10.18240/ijo.2023.08.01 -
The Ocular Surface Apr 2024Meibomian gland dysfunction (MGD) is a leading cause of dry eye disease and one of the most common ophthalmic conditions encountered in eye clinics worldwide. These...
Meibomian gland dysfunction (MGD) is a leading cause of dry eye disease and one of the most common ophthalmic conditions encountered in eye clinics worldwide. These holocrine glands are situated in the eyelid, where they produce specialized lipids, or meibum, needed to lubricate the eye surface and slow tear film evaporation - functions which are critical to preserving high-resolution vision. MGD results in tear instability, rapid tear evaporation, changes in local microflora, and dry eye disease, amongst other pathological entities. While studies identifying the mechanisms of MGD have generally focused on gland obstruction, we now know that age is a major risk factor for MGD that is associated with abnormal cell differentiation and renewal. It is also now appreciated that immune-inflammatory disorders, such as certain autoimmune diseases and atopy, may trigger MGD, as demonstrated through a T cell-driven neutrophil response. Here, we independently discuss the underlying roles of gland and immune related factors in MGD, as well as the integration of these two distinct mechanisms into a unified perspective that may aid future studies. From this unique standpoint, we propose a revised model in which glandular dysfunction and immunopathogenic pathways are not primary versus secondary contributors in MGD, but are fluid, interactive, and dynamic, which we likened to the Yin and Yang of MGD.
Topics: Humans; Dry Eye Syndromes; Meibomian Gland Dysfunction; Meibomian Glands; Tears
PubMed: 38224775
DOI: 10.1016/j.jtos.2024.01.004 -
Biochemical and Biophysical Research... Feb 2024To investigated the role of estrogen receptor-1 (ER-1) in maintaining homeostasis in ocular surface.
PURPOSE
To investigated the role of estrogen receptor-1 (ER-1) in maintaining homeostasis in ocular surface.
METHODS
ER-1-knockout (ER-1KO) mice were studied at 4 months of age. The ocular surface was examined using a slit lamp. Histological alterations in the meibomian gland (MG) and lacrimal gland (LG) were observed with H&E staining. Protein levels of P-ERK, peroxisome proliferator-activated receptor gamma (PPAR-γ), p-NFκB-P65, IL-1β, aquaporin 5 (AQP-5), fatty acid-binding protein 5 (Fabp5) and K10 were determined by immunofluorescence and Western blotting. Gene expressions of APO-F, APO-E, K10, ELOVL4, PPAR-γ, SCD-1, and SREBP1 were quantified by qPCR. Conjunctival (CJ) goblet cell alterations were detected by PAS staining. Lipid metabolism in MG and LG was assessed using LipidTox. Apoptosis in MG and LG was analyzed through the TUNEL assay.
RESULTS
Both male and female ER-1KO mice demonstrated increased corneal fluorescence staining scores. MG showed abnormal lipid metabolism and ductal dilation. LG displayed lipid deposition and reduced AQP-5 expression. CJ experienced goblet cell loss. MG, LG exhibited signs of inflammation and apoptosis.
CONCLUSION
ER1 is pivotal for ocular surface homeostasis in both genders of mice. ER1 deficiency induces inflammation and lipid deposition to MG and LG, culminating in dry eye-like manifestations on the ocular surface.
Topics: Animals; Female; Male; Mice; Dry Eye Syndromes; Inflammation; Lacrimal Apparatus; Meibomian Glands; Peroxisome Proliferator-Activated Receptors; Tears; Receptors, Estrogen
PubMed: 38241812
DOI: 10.1016/j.bbrc.2024.149526 -
BMJ Open Feb 2024The lipid layer of the tear film is critical to maintaining the integrity of the tear film and absence in the tear film lipid layer (TFLL) is one of the main causes of...
INTRODUCTION
The lipid layer of the tear film is critical to maintaining the integrity of the tear film and absence in the tear film lipid layer (TFLL) is one of the main causes of evaporative dry eye (EDE) in dry eye disease patients, resulting in excessive evaporation (so-called hyperevaporative dry eye). This study protocol will be designed to assess and compare the effects of intense pulsed light (IPL), heated eye mask (HEM), vectored thermal pulsation system (VTPS) and eyelid massage device (EMD) for improving signs and symptoms of EDE.
METHODS AND ANALYSIS
Patients with EDE will be randomly divided into IPL, HEM, VTPS and EMD groups and will be followed up for 6 weeks. The primary outcome measure will be non-invasive tear breakup time (NITBUT). The secondary outcome measures will include, TFLL score, meibomian gland quality and expressibility change from baseline conjunctivocorneal staining with fluorescein and lissamine, tear meniscus height, conjunctival hyperaemia (redness score) and ocular surface disease index questionnaire. Additionally, adverse events will be monitored and documented.
ETHICS AND DISSEMINATION
Ethics approval number: IRB(2023)K019.01. The findings will be shared regardless of the effect's direction.
TRIAL REGISTRATION NUMBER
NCT05923528.
Topics: Humans; Meibomian Glands; Dry Eye Syndromes; Tears; Fluorescein; Lipids; Randomized Controlled Trials as Topic
PubMed: 38413161
DOI: 10.1136/bmjopen-2023-078727 -
Acta Ophthalmologica Jun 2024One of the most common causes of blindness on a global scale is glaucoma. There is a strong association between glaucoma and increased intraocular pressure (IOP).... (Review)
Review
One of the most common causes of blindness on a global scale is glaucoma. There is a strong association between glaucoma and increased intraocular pressure (IOP). Because of this, adequate IOP-lowering is the most important treatment strategy, mostly through topical eyedrops. Well-functioning meibomian glands are paramount for maintaining a stable tear film, and their dysfunction is the most common cause of dry eye disease. There is a growing concern that both topical glaucoma medications themselves and their added preservatives damage the meibomian glands, and consequently, the ocular surface. Preserved topical glaucoma medications appear to cause dysfunction and atrophy of the meibomian glands. Upon comparison, preserved formulations caused more symptoms of dry eye, tear film instability, inflammatory changes and meibomian gland dropout than the preservative-free counterpart. However, although seemingly less detrimental, unpreserved alternatives may diminish glandular efficacy, and, depending on the active ingredient, lead to glandular death. This negatively impacts quality of life, adherence to treatment regimens and prognosis. In this review, we explore the available evidence regarding the effects of IOP-lowering eye drops on the meibomian glands.
PubMed: 38822682
DOI: 10.1111/aos.16728 -
International Ophthalmology Sep 2023We sought to investigate the association of meibomian gland morphology with lid margin abnormalities in patients with meibomian gland dysfunction.
PURPOSE
We sought to investigate the association of meibomian gland morphology with lid margin abnormalities in patients with meibomian gland dysfunction.
METHODS
This retrospective study included 368 eyes of 184 patients. Meibography was used to evaluate meibomian gland (MG) morphological features, such as dropout, distortion, thickened ratio and thinned ratio. Lid margin photography was used to evaluate lid margin abnormalities including orifice plugging, vascularity, irregularity and thickening. The association between MG morphological features and lid margin abnormalities was analyzed using a mixed linear model.
RESULTS
The study found a positive correlation between plugging of gland orifices grade and MG dropout grade in both the upper lids (B = 0.40, p = 0.007) and the lower lids (B = 0.55, p = 0.001). Plugging of gland orifices grade was also positively correlated to MG distortion grade in the upper lids (B = 0.75, p = 0.006). In the upper lids, MG thickened ratio increased first (B = 0.21, p = 0.003) and then decreased (B = - 0.14, p = 0.010) with a higher lid margin thickening grade. MG thinned ratio was negatively correlated with lid margin thickening (B = - 0.14, p = 0.002, B = - 0.13, p = 0.007). MG distortion grade decreased with lid margin thickening (B = - 0.61, p = 0.012).
CONCLUSION
Orifice plugging was correlated to meibomian gland distortion and dropout. Lid margin thickening was associated with meibomian gland thickened ratio, thinned ratio, and distortion. The study also suggested that distorted and thinned glands may be transitional phases between thickened glands and glands dropout.
Topics: Humans; Meibomian Glands; Meibomian Gland Dysfunction; Retrospective Studies; Photography; Eyelid Diseases; Tears; Dry Eye Syndromes
PubMed: 37140834
DOI: 10.1007/s10792-023-02721-2 -
Photobiomodulation, Photomedicine, and... Nov 2023The purpose of this study was to compare the effectiveness of optimal pulsed technology (OPT) and meibomian gland massage (MGM) in alleviating the signs and symptoms of... (Randomized Controlled Trial)
Randomized Controlled Trial
The purpose of this study was to compare the effectiveness of optimal pulsed technology (OPT) and meibomian gland massage (MGM) in alleviating the signs and symptoms of contact lens-related meibomian gland dysfunction (CL-MGD). This prospective, randomized, controlled study included 90 patients (180 eyes) diagnosed with CL-MGD and were assigned to the OPT group ( = 60 eyes), MGM group ( = 60 eyes), and control group ( = 60 eyes). All participants were examined at baseline (D0), day 21 (D21), and day 42 (D42) for the ocular surface disease index (OSDI), noninvasive tear break-up time (NITBUT), noninvasive tear meniscus height (NITMH), meibomian gland score (MGS), meibomian gland score (MGYSS), best-corrected visual acuity, and intraocular pressure. The OSDI scores and NITBUT improved after treatment in all the three groups. The OSDI scores in OPT and MGM groups were significantly lower compared with that in the control group at D21 and further decreased at D42. The NITBUT in OPT and MGM groups increased compared with the control group at D21 and further increased at D42, and the NITBUT in OPT group increased compared with the MGM group at D21 and D42. The MGYSS both improved after treatment in the OPT and MGM groups, The MGYSS in OPT and MGM groups decreased compared with the control group at D21 and further decreased at D42, and the MGYSS in the OPT group decreased compared with the MGM group at D21 and D42. The NITMH and MGS had no differences after treatment. Results imply that OPT or MGM treatment can be safely used to relieve symptoms of CL-MGD. In addition, OPT treatment was found to be more effective in improving the general stability of the tear-film in CL-MGD.
Topics: Humans; Meibomian Glands; Meibomian Gland Dysfunction; Prospective Studies; Massage; Contact Lenses
PubMed: 37976238
DOI: 10.1089/photob.2023.0054 -
Experimental Eye Research Sep 2023Acrolein is a highly reactive volatile toxic chemical that injures the eyes and many organs. It has been used in wars and terrorism for wounding masses on multiple...
Acrolein is a highly reactive volatile toxic chemical that injures the eyes and many organs. It has been used in wars and terrorism for wounding masses on multiple occasions and is readily accessible commercially. Our earlier studies revealed acrolein's toxicity to the cornea and witnessed damage to other ocular tissues. Eyelids play a vital role in keeping eyes mobile, moist, lubricated, and functional utilizing a range of diverse lipids produced by the Meibomian glands located in the upper and lower eyelids. This study sought to investigate acrolein's toxicity to eyelid tissues by studying the expression of inflammatory and lipid markers in rabbit eyes in vivo utilizing our reported vapor-cap model. The study was approved by the institutional animal care and use committees and followed ARVO guidelines. Twelve New Zealand White Rabbits were divided into 3 groups: Naïve (group 1), 1-min acrolein exposure (group 2), or 3-min acrolein exposure (group 3). The toxicological effects of acrolein on ocular health in live animals were monitored with regular clinical eye exams and intraocular pressure measurements and eyelid tissues post-euthanasia were subjected to H&E and Masson's trichrome histology and qRT-PCR analysis. Clinical eye examinations witnessed severely swollen eyelids, abnormal ocular discharge, chemosis, and elevated intraocular pressure (p < 0.001) in acrolein-exposed eyes. Histological studies supported clinical findings and exhibited noticeable changes in eyelid tissue morphology. Gene expression studies exhibited significantly increased expression of inflammatory and lipid mediators (LOX, PAF, Cox-2, and LTB4; p < 0.001) in acrolein-exposed eyelid tissues compared to naïve eyelid tissues. The results suggest that acrolein exposure to the eyes causes acute damage to eyelids by altering inflammatory and lipid mediators in vivo.
Topics: Rabbits; Animals; Acrolein; Meibomian Glands; Cornea; Lipids
PubMed: 37451567
DOI: 10.1016/j.exer.2023.109575