scholarly journals Inhibition of Aberrant α(1,2)-Fucosylation at Ocular Surface Ameliorates Dry Eye Disease

2021 ◽  
Vol 22 (15) ◽  
pp. 7863
Author(s):  
Chang Ho Yoon ◽  
Jin Suk Ryu ◽  
Jung Hwa Ko ◽  
Joo Youn Oh
Keyword(s):  
Dry Eye ◽  
Ocular Surface ◽  
Meibomian Gland ◽  
Cellular Adhesion ◽  
Dry Eye Disease ◽  
Eye Disease ◽  
Corneal Epithelial ◽  
Wide Range ◽  
Novel Target ◽  
Desiccating Stress

Fucosylation is involved in a wide range of biological processes from cellular adhesion to immune regulation. Although the upregulation of fucosylated glycans was reported in diseased corneas, its implication in ocular surface disorders remains largely unknown. In this study, we analyzed the expression of a fucosylated glycan on the ocular surface in two mouse models of dry eye disease (DED), the NOD.B10.H2b mouse model and the environmental desiccating stress model. We furthermore investigated the effects of aberrant fucosylation inhibition on the ocular surface and DED. Results demonstrated that the level of type 2 H antigen, an α(1,2)-fucosylated glycan, was highly increased in the cornea and conjunctiva both in NOD.B10.H2b mice and in BALB/c mice subjected to desiccating stress. Inhibition of α(1,2)-fucosylation by 2-deoxy-D-galactose (2-D-gal) reduced corneal epithelial defects and increased tear production in both DED models. Moreover, 2-D-gal treatment suppressed the levels of inflammatory cytokines in the ocular surface and the percentages of IFN-γ+CD4+ cells in draining lymph nodes, whereas it did not affect the number of conjunctival goblet cells, the MUC5AC level or the meibomian gland area. Together, the findings indicate that aberrant fucosylation underlies the pathogenesis of DED and may be a novel target for DED therapy.

scholarly journals Desiccating stress-induced disruption of ocular surface immune tolerance drives dry eye disease

2016 ◽  
Vol 184 (2) ◽  
pp. 248-256 ◽  
Author(s):  
M. Guzmán ◽  
I. Keitelman ◽  
F. Sabbione ◽  
A. S. Trevani ◽  
M. N. Giordano ◽  
...  
Keyword(s):  
Dry Eye ◽  
Immune Tolerance ◽  
Ocular Surface ◽  
Dry Eye Disease ◽  
Eye Disease ◽  
Desiccating Stress

scholarly journals Meibomian Gland Dysfunction

2019 ◽  
Vol 35 (1) ◽  
Author(s):  
Sameera Irfan
Keyword(s):  
Dry Eye ◽  
Ocular Surface ◽  
Treatment Strategies ◽  
Tear Film ◽  
Meibomian Gland ◽  
Dry Eye Disease ◽  
Meibomian Gland Dysfunction ◽  
Eye Disease ◽  
Treatment Protocols ◽  
Dry Eyes

Dry eyes is a common, chronic condition that has a prevalence of about 5- 50%.1 According to the Dry Eye Workshop II report (DEWS II report), published in 2017, the updated definition of Dry Eye Disease is, “a multifactorial disease of the ocular surface characterised by a loss of homeostasis of the tear film, and accompanied by ocular symptoms, in which tear film instability and hyper-osmolarity, ocular surface inflammation and damage, and neurosensory abnormalities play etiological roles.” The Tear Film & Ocular Surface Society (TFOS) released their report on the international work on Meibomian Gland Dysfunction (MGD)2 in 2011, which defined MGD, classified it and considered it as the primary cause of dry eye disease worldwide. Previously dry eye disease was considered as an aqueous deficiency problem, but after this report by TFOS, there is a paradigm shift towards “not producing enough lipids to retain the tears that are being produced”. This has led to a huge impact on the treatment protocols which were previously focused on managing the sequelae and symptoms of dry eyes rather than targeting directly on the underlying cause, the MGD. It has now been accepted worldwide that dry eye occurs when the ocular surface system cannot adequately protect itself from the desiccating stress due to the lack of a healthy meibomian gland secretion. This article is mainly focussed on the Meibomian Gland Dysfunction, discussing the normal anatomy of the glands, how they are affected by disease, its implications on the ocular surface and finally, the various treatment strategies. Key words: Blepharitis, Dry eyes, Meibomian gland dysfunction, blepharospasm.

scholarly journals Antioxidant Effects of the Prenylated Flavonoid, Xanthohumol, on Corneal Epithelial Cells in Experimental Dry Eye Disease

2021 ◽  
Author(s):  
Anita Kirti Ghosh ◽  
Rubina Thapa ◽  
Harsh Nilesh Hariani ◽  
Michael Volyanyuk ◽  
Karoline Anne Orloff ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Epithelial Cells ◽  
Dry Eye ◽  
Ocular Surface ◽  
Dry Eye Disease ◽  
Eye Disease ◽  
Related Factor ◽  
Corneal Epithelial Cells ◽  
Corneal Epithelial

Elevated levels of oxidative stress in the corneal epithelium contribute to the progression of dry eye disease pathology. Previous studies have shown that antioxidant therapeutic intervention is a promising avenue to reduce disease burden and slow disease progression. In this study, we evaluated the pharmacological efficacy of Xanthohumol in preclinical models for dry eye disease. Xanthohumol is a naturally occurring prenylated chalconoid that promotes the transcription of phase II antioxidant enzymes. Xanthohumol exerted a dose-response in preventing tert-butylhydroxide-induced loss of cell viability in human corneal epithelial (HCE-T) cells and resulted in a significant increase in expression of nuclear factor erythroid 2-related factor 2 (Nrf2), the master regulator of the endogenous antioxidant system. Xanthohumol-encapsulating poly(lactic-co-glycolic acid) nanoparticles (PLGA NP) were cytoprotective against oxidative stress in vitro, and significantly reduced corneal fluorescein staining in the mouse desiccating stress/ scopolamine model for dry eye disease in vivo by reducing oxidative stress-associated DNA damage in corneal epithelial cells. PLGA NP represent a safe and efficacious drug delivery vehicle for hydrophobic small molecules to the ocular surface. Optimization of NP-based antioxidant formulations with the goal to minimize instillation frequency may represent future therapeutic options for dry eye disease and related ocular surface disease.

scholarly journals Poly(lactic-co-glycolic acid) Nanoparticles Encapsulating the Prenylated Flavonoid, Xanthohumol, Protect Corneal Epithelial Cells from Dry Eye Disease-Associated Oxidative Stress

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1362
Author(s):  
Anita Kirti Ghosh ◽  
Rubina Thapa ◽  
Harsh Nilesh Hariani ◽  
Michael Volyanyuk ◽  
Sean David Ogle ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Epithelial Cells ◽  
Dry Eye ◽  
Ocular Surface ◽  
Glycolic Acid ◽  
Dry Eye Disease ◽  
Eye Disease ◽  
Corneal Epithelial Cells ◽  
Corneal Epithelial

Oxidative stress is a known contributor to the progression of dry eye disease pathophysiology, and previous studies have shown that antioxidant intervention is a promising therapeutic approach to reduce the disease burden and slow disease progression. In this study, we evaluated the pharmacological efficacy of the naturally occurring prenylated chalconoid, xanthohumol, in preclinical models for dry eye disease. Xanthohumol acts by promoting the transcription of phase II antioxidant enzymes. In this study, xanthohumol prevented tert-butyl hydroperoxide-induced loss of cell viability in human corneal epithelial (HCE-T) cells in a dose-dependent manner and resulted in a significant increase in expression of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), the master regulator of phase II endogenous antioxidant enzymes. Xanthohumol-encapsulating poly(lactic-co-glycolic acid) nanoparticles (PLGA NP) were cytoprotective against oxidative stress in vitro, and significantly reduced ocular surface damage and oxidative stress-associated DNA damage in corneal epithelial cells in the mouse desiccating stress/scopolamine model for dry eye disease in vivo. PLGA NP represent a safe and efficacious drug delivery vehicle for hydrophobic small molecules to the ocular surface. Optimization of NP-based antioxidant formulations with the goal to minimize instillation frequency may represent future therapeutic options for dry eye disease and related ocular surface disease.

scholarly journals Diagnostic Performance of a Novel Noninvasive Workup in the Setting of Dry Eye Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Luca Vigo ◽  
Marco Pellegrini ◽  
Federico Bernabei ◽  
Francesco Carones ◽  
Vincenzo Scorcia ◽  
...  
Keyword(s):  
Dry Eye ◽  
Ocular Surface ◽  
Diagnostic Performance ◽  
Pearson Correlation ◽  
Area Under The Curve ◽  
Meibomian Gland ◽  
Dry Eye Disease ◽  
Eye Disease ◽  
Continuous Variables ◽  
Cross Sectional

Purpose. To evaluate the diagnostic performance of a novel noninvasive automated workup employed for the diagnosis of dry eye disease (DED). Methods. One hundred patients with mild to moderate DED and 100 matched control subjects were enrolled in this cross-sectional study. Ocular surface examinations were carried out by means of IDRA Plus (SBM Sistemi, Turin, Italy), which allows the automated evaluation of noninvasive breakup time (NIBUT), lipid layer thickness (LLT), tear meniscus height (TMH), infrared meibography for the measurement of meibomian gland loss (MGL), and blinking analysis. Continuous variables were compared between patients with DED and controls by using the Mann–Whitney U test. The area under the curve (AUC) of receiver operating characteristic curves was calculated. The correlations between ocular surface parameters were evaluated with Pearson correlation analysis. Results. Patients with DED showed significantly lower values of NIBUT, LLT, and TMH compared to controls (6.9 ± 2.5 vs 10.4 ± 2.4 s, P  < 0.001; 64.6 ± 20.3 vs 73.4 ± 21.9 nm, P  = 0.003; 0.231 ± 0.115 vs 0.289 ± 0.164, P  = 0.012, respectively). Conversely, no significant differences were observed for MGL and blinking analysis (both P  > 0.05). NIBUT had the highest diagnostic power (AUC = 0.841, sensitivity = 0.89, and specificity = 0.69), followed by LLT (AUC = 0.621, sensitivity = 0.89, and specificity = 0.55), TMH (AUC = 0.606, sensitivity = 0.57, and specificity = 0.63), blink analysis (AUC = 0.533, sensitivity = 0.48, and specificity = 0.59), and MGL (AUC = 0.531, sensitivity = 0.54, and specificity = 0.48). In patients with DED, NIBUT showed a significant correlation with TMH (R = 0.347, P  = 0.002) and blinking analysis (R = 0.356, P  < 0.001), while blinking analysis was negatively correlated with MGL (R = −0.315, P  = 0.008). Conclusions. The automated noninvasive workup validated in this study may be a useful tool for reaching a noninvasive diagnosis of DED with a good performance, especially for NIBUT.

scholarly journals Meibomian Gland Dysfunction: Intense Pulsed Light Therapy in Combination with Low-Level Light Therapy as Rescue Treatment

Medicina ◽  
2021 ◽  
Vol 57 (6) ◽  
pp. 619
Author(s):  
Leonidas Solomos ◽  
Walid Bouthour ◽  
Ariane Malclès ◽  
Gabriele Thumann ◽  
Horace Massa
Keyword(s):  
Dry Eye ◽  
Ocular Surface ◽  
Light Therapy ◽  
Meibomian Gland ◽  
Dry Eye Disease ◽  
Meibomian Gland Dysfunction ◽  
Eye Disease ◽  
Low Level Light Therapy ◽  
Rescue Treatment ◽  
Intense Pulsed Light Therapy

Background and Objectives: Evaporative dry eye disease is frequently associated with meibomian gland dysfunction. Patients are often unhappy because of daily drops, care burden, and suboptimal conventional treatments. In this study, we assessed the efficacy of a novel device, the Eye-light®, a combination of intense pulsed light therapy and low-level light therapy, as a novel treatment for meibomian gland dysfunction and dry eye disease. Materials and Methods: This was a retrospective, single-center study carried out over a 6-week period, in which 22 eyes from 11 patients were included. Each patient received four combined light therapy treatment sessions, once weekly over 4 weeks. Patients underwent a clinical examination and filled out a standardized questionnaire to evaluate symptoms one week prior to treatment, and one week after the fourth session. Results: Combined light therapy improved several ocular surface outcome measures in our patients. This study demonstrates that this adjunctive treatment significantly improves the ocular surface and quality of life of patients with dry eye disease and meibomian gland dysfunction. Conclusions: Combined light therapy may be included in meibomian gland dysfunction treatment protocols as an adjunctive rescue treatment.

scholarly journals Sex Hormones Related Ocular Dryness in Breast Cancer Women

2021 ◽  
Vol 10 (12) ◽  
pp. 2620
Author(s):  
Antonella Grasso ◽  
Antonio Di Zazzo ◽  
Giuseppe Giannaccare ◽  
Jaemyoung Sung ◽  
Takenori Inomata ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Sex Hormones ◽  
Dry Eye ◽  
Ocular Surface ◽  
Meibomian Gland ◽  
Dry Eye Disease ◽  
Eye Disease ◽  
Hormonal Imbalance ◽  
Gland Function

Background: Dry eye syndrome (DES) is strictly connected to systemic and topical sex hormones. Breast cancer treatment, the subsequent hormonal therapy, the subsequent hyperandrogenism and the early sudden menopause, may be responsible for ocular surface system failure and its clinical manifestation as dry eye disease. This local dryness is part of the breast cancer iatrogenic dryness, which affects overall mucosal tissue in the fragile population of those with breast cancer. Methods: A literature review regarding the role of sex hormone changes and systemic hormonal replacement treatments (SHRT) in DES available on PubMed and Web of Science was made without any restriction of language. Results: Androgens exert their role on the ocular surface supporting meibomian gland function and exerting a pro-sebaceous effect. Estrogen seems to show a pro/inflammatory role on the ocular surface, while SHRT effects on dry eye are still not well defined, determining apparently contradictory consequences on the ocular surface homeostasis. The role of sex hormones on dry eye pathogenesis is most likely the result of a strict crosstalk between the protective androgens effects and the androgen-modulating effects of estrogens on the meibomian glands. Conclusions: Patients with a pathological or iatrogenic hormonal imbalance, such as in the case of breast cancer, should be assessed for dry eye disease, as well as systemic dryness, in order to restore their social and personal quality of life.

scholarly journals Meibomian gland dysfunction and keratopathy are associated with dry eye disease in aniridia

2018 ◽  
Vol 103 (1) ◽  
pp. 119-124 ◽  
Author(s):  
Erlend Christoffer Sommer Landsend ◽  
Hilde Røgeberg Pedersen ◽  
Øygunn Aass Utheim ◽  
Jiaxin Xiao ◽  
Muhammed Yasin Adil ◽  
...  
Keyword(s):  
Dry Eye ◽  
Ocular Surface ◽  
Tear Film ◽  
Vital Staining ◽  
Meibomian Gland ◽  
Dry Eye Disease ◽  
Eye Disease ◽  
Control Group ◽  
Healthy Controls ◽  
Congenital Aniridia

AimsTo investigate the aetiology and characteristics of dry eye disease (DED) in a Nordic cohort of patients with congenital aniridia.MethodsThirty-four Norwegian and one Danish subject with congenital aniridia and 21 healthy controls were examined. All subjects underwent an extensive dry eye examination, including evaluation of meibomian glands (MGs) by meibography, measurement of tear production and tear film osmolarity and grading of vital staining of the ocular surface. Moreover, slit-lamp biomicroscopy was undertaken, including grading of aniridia-associated keratopathy (AAK).ResultsMean tear film osmolarity was significantly higher (314±11 mOsmol/L) in patients with aniridia compared with the healthy control group (303±11 mOsmol/L, p=0.002). Vital staining score was higher in the aniridia group (4.3±3.0) compared with healthy controls (2.4±1.6, p=0.02). The degree of staining correlated positively with the stage of AAK (r=0.44, p=0.008) and negatively with corneal sensitivity (r=−0.45, p=0.012). Number of expressible MGs was lower in aniridia subjects (2.9±1.6) than in controls (4.0±1.3, p=0.007). MG loss, staged from 0 to 3, was higher in the aniridia group than in the control group, both in upper eyelid (0.86±0.89 vs 0.10±0.31, p=0.001) and lower eyelid (0.94±0.73 vs 0.30±0.47, p=0.003). Computerised analyses showed thinning (p=0.004) and lower density (p<0.001) of the MGs compared with the healthy population.ConclusionsPatients with congenital aniridia demonstrate increased tear film osmolarity, ocular surface staining, loss of MGs and lower MG expressibility. We conclude that meibomian gland dysfunction and keratopathy are related to development of DED in aniridia.

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