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Experimental Eye Research Apr 2024The accumulation of oleic acid (OA) in the meibum from patients with meibomian gland dysfunction (MGD) suggests that it may contribute to meibomian gland (MG) functional...
The accumulation of oleic acid (OA) in the meibum from patients with meibomian gland dysfunction (MGD) suggests that it may contribute to meibomian gland (MG) functional disorder, as it is a potent stimulator of acne-related lipogenesis and inflammation in sebaceous gland. Therefore, we investigate whether OA induces lipogenesis and inflammasome activation in organotypic cultured mouse MG and human meibomian gland epithelial cells (HMGECs). Organotypic cultured mouse MG and HMGECs were exposed to OA or combinations with specific AMPK agonists 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR). Lipogenic status, ductal keratinization, squamous metaplasia, NLRP3/ASC/Caspase-1 inflammasome activation, proinflammatory cytokine IL-1β production, and AMPK pathway phosphorylation in MG were subsequently examined by lipid staining, immunofluorescence staining, immunohistochemical staining, ELISA assay, and Western blot analyses. We found that OA significantly induced lipid accumulation, ductal keratinization, and squamous metaplasia in organotypic cultured MG, as evidenced by increased lipids deposition within acini and duct, upregulated expression of lipogenic proteins (SREBP-1 and HMGCR), and elevation of K10/Sprr1b. Additionally, OA induced NLRP3/ASC/Caspase-1 inflammasome activation, cleavage of Caspase-1, and production of downstream proinflammatory cytokine IL-1β. The findings of lipogenesis and NLRP3-related proinflammatory response in OA-stimulated HMGECs were consistent with those in organotypic cultured MG. OA exposure downregulated phospho-AMPK in two models, while AICAR treatment alleviated lipogenesis by improving AMPK/ACC phosphorylation and SREBP-1/HMGCR expression. Furthermore, AMPK amelioration inhibited activation of the NLRP3/ASC/Caspase-1 axis and secretion of IL-1β, thereby relieving the OA-induced proinflammatory response. These results demonstrated that OA induced lipogenic disorder and NLRP3 inflammasome activation in organotypic cultured mouse MG and HMGECs by suppressing the AMPK signaling pathway, indicating OA may play an etiological role in MGD.
Topics: Humans; Mice; Animals; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; Sterol Regulatory Element Binding Protein 1; Oleic Acid; Meibomian Glands; AMP-Activated Protein Kinases; Lipogenesis; Epithelial Cells; Caspase 1; Cytokines; Metaplasia; Carcinoma, Squamous Cell; Interleukin-1beta
PubMed: 38453039
DOI: 10.1016/j.exer.2024.109851 -
Clinical & Experimental Ophthalmology Mar 2024Graft-versus-host disease (GVHD) is a systemic disease that can affect multiple organs as a consequence of an allogeneic haematopoietic stem cell transplant. One organ... (Review)
Review
Graft-versus-host disease (GVHD) is a systemic disease that can affect multiple organs as a consequence of an allogeneic haematopoietic stem cell transplant. One organ system that is often affected in GVHD is the eyes. Ocular GVHD (oGVHD) may involve various structures within the eye including the lacrimal glands, eyelids, conjunctiva, cornea, and nasolacrimal ducts, and is a source of morbidity in patients with GVHD. Common presenting features of GVHD overlap with dry eye disease (DED), including decreased tear production, epithelial disruption, and Meibomian gland dysfunction (MGD). In this review, we aim to compare oGVHD and DED to better understand the similarities and differences between the conditions, with a focus on pathophysiology, risk factors, clinical features, and treatments.
Topics: Humans; Dry Eye Syndromes; Cornea; Conjunctiva; Graft vs Host Disease; Meibomian Gland Dysfunction; Hematopoietic Stem Cell Transplantation
PubMed: 38204146
DOI: 10.1111/ceo.14347 -
BMJ Open Ophthalmology Dec 2023To investigate the clinical outcomes and antimicrobial activity of an hypochlorous acid hygiene solution compared with hyaluronic acid wipes for blepharitis treatment in... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND/AIMS
To investigate the clinical outcomes and antimicrobial activity of an hypochlorous acid hygiene solution compared with hyaluronic acid wipes for blepharitis treatment in patients with dry eye disease (DED).
METHODS
This study involved 48 eyes of 48 patients affected by blepharitis with mild to moderate DED. 24 patients were treated with a hypochlorous acid hygiene solution (HOCL group) and 24 patients were treated with hyaluronic acid wipes (HYAL group) for a period of 4 weeks. The following clinical outcomes were assessed before (V0) and after the treatment period (V1): non-invasive keratograph break up time (NIK-BUT), tear film BUT (TF-BUT) tear meniscus height (TMH), Keratograph meibography, Meibomian Gland Yield Secretion Score (MGYSS), Corneal Staining Score (CSS), Schirmer test I, Keratograph conjunctival redness score and Ocular Surface Disease Index (OSDI). Moreover, microbiological analysis of upper and lower eyelid margins was performed at V0 both before and 5 min after treatment.
RESULTS
After 1-month NIK-BUT and TF-BUT significantly increased in HOCL group, while they did not show a statistically significant difference in HYAL group compared with baseline. OSDI, TMH and MGYSS showed a significant difference in both groups, while Schirmer test, meibography, CSS and conjunctival redness score did not significantly change in both groups. Bacterial load showed a significant reduction in both groups, more pronounced in HOCL group compared with HYAL group.
CONCLUSIONS
Hypochlorous acid hygiene solution can be securely employed in blepharitis treatment considering the satisfying clinical outcomes and antimicrobial activity compared with hyaluronic acid wipes.
Topics: Humans; Hypochlorous Acid; Prospective Studies; Hyaluronic Acid; Meibomian Glands; Blepharitis; Hygiene; Anti-Infective Agents
PubMed: 38088255
DOI: 10.1136/bmjophth-2022-001209 -
Graefe's Archive For Clinical and... Feb 2024To explore the long-term course of patients with meibomian gland dysfunction (MGD), and to analyse potential factors affecting the recovery of meibomian gland (MG)...
PURPOSE
To explore the long-term course of patients with meibomian gland dysfunction (MGD), and to analyse potential factors affecting the recovery of meibomian gland (MG) dropout.
METHODS
Seventy-nine MGD patients (79 eyes) aged 36.03±15.78 years old who underwent more than one year of follow-up were enrolled in this retrospective study. Corneal fluorescein staining (CFS), tear meniscus height (TMH), noninvasive breakup time (NIBUT), and noncontact meibography at baseline and last visit were collected and analysed. Then an automatic MG analyzer was used to measure the morphological and functional parameters of MGs, including their area ratio (AR), tortuosity index (TI), and signal index (SI). The patients whose AR increased by more than 5% were defined as MG improvement, and AR decreased by more than 5% was MG worsening.
RESULTS
A total of 79 patients (79 eyes) were assessed with at least 1-year of follow-up. More than 1/3 of MGD patients (27 eyes, 34.2%) underwent MG improvement, and 30.4% of MGs became worsened. Age (P=0.002), gender (P<0.001), IPL treatment (P=0.013), the change of CFS (P=0.0015), and the recovery of SI (P=0.035) showed significant differences among different recovery groups. Age(P<0.001), female sex (P=0.003), ΔCFS (P<0.001), AR at baseline (P<0.001) were negative correlation with AR recovery, and the change of SI (P=0.003) and IPL treatment (P=0.003) had a positive correlation with it. Among them, age (P=0.038), the change of CFS (P=0.004), and AR at baseline (P=0.007) were confirmed as negatively correlated factors predicting the long-term change of the MG.
CONCLUSION
Although the MGD treatment has continued for more than 1 year, only 34.2% of MGD patients were observed to undergo MG improvement. Younger patients and patients with better CFS recovery seem to have more opportunities to improve their MGs.
Topics: Humans; Female; Young Adult; Adult; Middle Aged; Meibomian Glands; Meibomian Gland Dysfunction; Retrospective Studies; Tears; Dry Eye Syndromes
PubMed: 37650897
DOI: 10.1007/s00417-023-06210-1 -
Investigative Ophthalmology & Visual... Dec 2023Hyperkeratinization of meibomian gland (MG) ducts is currently recognized as the primary pathologic mechanism of meibomian gland dysfunction (MGD). This research figured...
PURPOSE
Hyperkeratinization of meibomian gland (MG) ducts is currently recognized as the primary pathologic mechanism of meibomian gland dysfunction (MGD). This research figured out a method to isolate the MG ducts and established a novel system to culture the human meibomian gland ductal cells (HMGDCs) for investigating the process of MGD.
METHODS
The MG ducts were obtained from the eyelids of recently deceased donors and subjected to enzymatic digestion. The acini were then removed to isolate independent ducts. These MG ducts were subsequently cultivated on Matrigel-coated wells and covered with a glass plate to obtain HMGDCs. The HMGDCs were further cultivated until passage 2, and when they reached 60% confluence, they were treated with IL-1β and rosiglitazone for a duration of 48 hours. Immunofluorescence staining and Western blot techniques were employed to identify ductal cells and analyze the effects of IL-1β on HMGDCs in an in vitro setting.
RESULTS
Ophthalmic micro-forceps and insulin needles can be employed for the purpose of isolating ducts. Within this particular culture system, the rapid expansion of HMGDCs occurred in close proximity to the duct tissue. MG ducts specifically expressed keratin 6 (Krt6) and hardly synthesized lipids. Furthermore, the expression of Krt6 was significantly higher (P < 0.0001) in HMGDCs compared to human meibomian gland cells. Upon treatment with IL-1β, HMGDCs exhibited an overexpression of keratin 1, which was effectively blocked by the administration of rosiglitazone.
CONCLUSIONS
The present study successfully isolated human MG ducts and cultured HMGDCs, providing a valuable in vitro model for investigating the mechanism of MGD. Additionally, the potential therapeutic efficacy of rosiglitazone in treating hyperkeratinization of ducts in patients with MGD was identified.
Topics: Humans; Meibomian Glands; Rosiglitazone; Meibomian Gland Dysfunction; Blotting, Western; Cells, Cultured; Interleukin-1beta; Tears; Eyelid Diseases
PubMed: 38133507
DOI: 10.1167/iovs.64.15.29 -
Current Eye Research May 2024In this review, we aimed to investigate the literature on sex-specific prevalence of meibomian gland dysfunction (MGD) and to determine whether women or men are more at... (Review)
Review
PURPOSE
In this review, we aimed to investigate the literature on sex-specific prevalence of meibomian gland dysfunction (MGD) and to determine whether women or men are more at risk for MGD.
METHODS
A search was conducted on PubMed using the terms: .
RESULTS
Twenty-four relevant studies on MGD prevalence were identified, including 10 population-based and 14 hospital-based studies. Among the population-based studies, five studies reported higher rates among men, three studies found no differences, and one study observed higher rates among women. In the hospital-based studies, 10 studies reported no difference, two found higher rates among men, and one found higher among women. In the reviewed literature, there was a considerable variation between studies in terms of quality, sample size, age ranges, diagnostic criteria.
CONCLUSIONS
While most of the population-based studies suggest a higher prevalence among men, the majority of clinic-based studies show no significant difference. Further research with larger samples and standardized criteria is needed to determine whether men are indeed more susceptible to MGD.
Topics: Humans; Male; Female; Meibomian Gland Dysfunction; Eyelid Diseases; Prevalence; Sex Characteristics; Meibomian Glands; Tears; Dry Eye Syndromes
PubMed: 38196124
DOI: 10.1080/02713683.2023.2301325 -
Molecular Vision 2023The purpose of this study was to explore the effects of a PGF analog, latanoprost, and its preservative, benzalkonium chloride (BAK), on the cell viability and lipidomic...
Evaluation of the effects of latanoprost and benzalkonium chloride on the cell viability and nonpolar lipid profile produced by human meibomian gland epithelial cells in culture.
PURPOSE
The purpose of this study was to explore the effects of a PGF analog, latanoprost, and its preservative, benzalkonium chloride (BAK), on the cell viability and lipidomic expression of immortalized human meibomian gland epithelial cells (HMGECs).
METHODS
Differentiated HMGECs were exposed to latanoprost (0.05 to 50 µg/ml), BAK (0.2 to 200 µg/ml), or combined latanoprost-BAK (0.05-0.2 to 50-200 µg/ml). EP- and FP-type receptors, the cognate receptors of PGE and PGF, were inhibited, thereby sparing and isolating the function of each receptor to one condition. Cell viability was assessed by ATP quantitation, and lipid extracts were analyzed by ESI-MSMS with a Triple TOF 5600 Mass Spectrometer (SCIEX, Framingham, MA) using SCIEX LipidView 1.3.
RESULTS
Latanoprost and BAK were found to be lethal to HMGECs at the highest concentrations (p < 0.001 for both). The cytotoxicity of latanoprost was mediated through FP- and EP-independent mechanisms. Both latanoprost and BAK significantly modulated the lipidomic expression of several cholesteryl esters (8% and 30%, respectively) and triacylglycerols (10% and 12%, respectively). The combined latanoprost-BAK agent appeared to be no more toxic and to only negligibly alter the lipid profile relative to its individual components.
CONCLUSIONS
The use of latanoprost and BAK in glaucoma may alter the viability of the meibomian glands and their lipid expression in vivo. Sublethal concentrations of BAK appear to modulate meibum lipid expression, particularly in relation to sterol biosynthesis. Non-preserved latanoprost had less cytotoxicity at lower doses and fewer lipidomic effects compared to BAK, further strengthening the argument in favor of BAK-free pharmaceutical preparations.
Topics: Humans; Benzalkonium Compounds; Cell Survival; Latanoprost; Meibomian Glands; Epithelial Cells
PubMed: 38264609
DOI: No ID Found -
European Journal of Ophthalmology May 2024To demonstrate that intense pulsed light therapy (IPL) of the upper and lower eyelids with meibomian gland expression (MGX) is effective in improving dry eye disease due...
PURPOSE
To demonstrate that intense pulsed light therapy (IPL) of the upper and lower eyelids with meibomian gland expression (MGX) is effective in improving dry eye disease due to meibomian gland dysfunction (MGD).
METHODS
Patients with ocular discomfort (Ocular Surface Disease Index -OSDI- above 13) and signs of MGD were recruited. All patients underwent OSDI, visual acuity (VA), intraocular pressure, Schirmer test, meibography, non-invasive tear breakup time (NITBUT), slit-lamp examination (corneal and conjunctival staining, hyperemia, gland expressibility, and meibum quality), tear osmolarity and lipid layer thickness. IPL was performed with Optima IPL (Lumenis Ltd.) following a standardized protocol on upper and lower eyelids of both eyes, with inferior eyelid MGX. Patients received four sessions separated by two weeks each. Four weeks after, examinations were repeated.
RESULTS
160 patients (320 eyes) were included, of which 108 (67.5%) were women and mean age was 59.2 ± 15.08 (range 20-89). After four sessions, VA, OSDI, tear osmolarity, lipid layer thickness, NITBUT, hyperemia, corneal and conjunctival staining, gland expressibility, meibum quality, inferior eyelid Meiboscore and Schirmer test improved (all, p < 0.027). Changes in OSDI, initial and average NITBUT increased with dry eye disease severity (according to OSDI). Increased pre-treatment OSDI, hyperemia, corneal and conjunctival staining and Schirmer test were associated with an improvement in OSDI (all, p < 0.040). No adverse events were noted.
CONCLUSIONS
The combination of IPL on upper and lower eyelids with MGX is safe and effective for the treatment of MGD. Patients with severe dry eye disease present greater improvements.
Topics: Humans; Female; Meibomian Gland Dysfunction; Middle Aged; Male; Prospective Studies; Aged; Adult; Tears; Meibomian Glands; Aged, 80 and over; Intense Pulsed Light Therapy; Young Adult; Visual Acuity; Treatment Outcome; Dry Eye Syndromes; Eyelids; Osmolar Concentration; Intraocular Pressure
PubMed: 37671407
DOI: 10.1177/11206721231199121 -
[Zhonghua Yan Ke Za Zhi] Chinese... Nov 2023Meibomian gland dysfunction (MGD) is a common ocular surface disease. In recent years, the meibomian gland-related examination and treatment technologies have evolved...
Meibomian gland dysfunction (MGD) is a common ocular surface disease. In recent years, the meibomian gland-related examination and treatment technologies have evolved rapidly. In order to further optimize the diagnostic process of MGD in China and improve the treatment efficiency of MGD, the Chinese Branch of the Asian Dry Eye Society has organized relevant experts to discuss the clinical characteristics of MGD in China and the progress of research at home and abroad. Based on the expert consensus formed in 2017, the updated consensus opinions have been developed for clinical physicians to refer to in the diagnosis and management of MGD.
Topics: Humans; Consensus; Dry Eye Syndromes; Eyelid Diseases; Meibomian Gland Dysfunction; Meibomian Glands; Tears
PubMed: 37936356
DOI: 10.3760/cma.j.cn112142-20230822-00054 -
Cell & Bioscience Jul 2023Ectodysplasin-A (EDA), a skin-specific TNF ligand, interacts with its membrane receptor EDAR to trigger EDA signaling in skin appendage formation. Gene mutations in EDA...
BACKGROUND
Ectodysplasin-A (EDA), a skin-specific TNF ligand, interacts with its membrane receptor EDAR to trigger EDA signaling in skin appendage formation. Gene mutations in EDA signaling cause Anhidrotic/Hypohidrotic Ectodermal Dysplasia (A/HED), which affects the formation of skin appendages including hair, teeth, and several exocrine glands.
RESULTS
We report that EDA triggers the translocation of its receptor EDAR from a cytosolic compartment into the plasma membrane. We use protein affinity purification to show that upon EDA stimulation EDAR associates with SNAP23-STX6-VAMP1/2/3 vesicle trafficking complexes. We find that EDA-dependent PKA activation is critical for the association. Notably, either of two HED-linked EDAR mutations, T346M and R420W, prevents EDA-induced EDAR translocation; and both EDA-induced PKA activation and SNAP23 are required for Meibomian gland (MG) growth in a skin appendage model.
CONCLUSIONS
Overall, in a novel regulatory mechanism, EDA increases plasma membrane translocation of its own receptor EDAR, augmenting EDA-EDAR signaling in skin appendage formation. Our findings also provide PKA and SNAP23 as potential targets for the intervention of HED.
PubMed: 37430358
DOI: 10.1186/s13578-023-01082-8