The Level of Inflammatory Tear Cytokines is Elevated in Congenital Aniridia and Associated with Meibomian Gland Dysfunction

Landsend, Erlend Christoffer Sommer; Utheim, Øygunn Aass; Pedersen, Hilde Røgeberg; Aass, Hans Christian Dalsbotten; Lagali, Neil; Dartt, Darlene A.; Baraas, Rigmor C.; Utheim, Tor Paaske

doi:10.1167/iovs.18-24027

Cited by 44 publications

(30 citation statements)

References 32 publications

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“…Some previous studies have demonstrated the role of MIP-1α in dysfunctional tear syndrome, the increasing level of MIP-1α has correlation with parameters for meibomian gland dysfunction (MGD) in congenital aniridia, including increasing atrophy of meibomian glands, and shorter break-up time of the tear film [ 36 ]. EGF, a pleiotropic cytokine secreted by the lacrimal gland, is essential for maintaining homeostasis of the ocular surface epithelia and to stimulate proliferation, migration, adhesion of corneal epithelial cells during wound healing.…”

Section: Discussionmentioning

confidence: 99%

Tear Luminex Analysis in Dry Eye Patients

Zhao

et al. 2018

Med Sci Monit

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BackgroundThe purpose of this study was to analyze tear inflammatory cytokines of different subclasses of dry eye disease (DED) patients using Luminex technology.Material/MethodsForty-five DED patients including 20 Sjogren syndrome aqueous tear deficiency (SS-ATD) patients, 20 non-Sjogren syndrome aqueous tear deficiency (NSS-ATD) patients, 15 meibomian gland dysfunction (MGD) patients, and 15 normal participants were enrolled in this study. Concentrations of 11 inflammatory cytokines in tear samples of study participants were measured by Luminex assay; ELISA assay was further applied for validation.ResultsThe levels of cytokines were mostly increased (TNF-α, IL-1α, IL-1β, IL-6, IL-8, IL-12P70, IL-13, IFN-γ, and MIP-1α) in DED patients compared with normal participants. And the levels of TNF-α, IL-6, IL-8, and IL-12P70 were significantly elevated in tears of the patient groups compared to tears of participants in the normal group (P<0.05). Statistical differences were also observed among the patient groups (SS-ATD, NSS-ATD, and MGD) for the level of IL-8 and TNF-α. The results of ELISA assay demonstrated the consistence with Luminex assay, confirming the practicality of Luminex technology for the analysis of multiple cytokines in DED patient tears.ConclusionsThe levels of inflammatory cytokines were mostly elevated in DED patients, and statistical differences of some cytokines were also found between SS-ATD, NSS-ATD, and MGD groups, suggesting that inflammatory cytokines could be potential supplements for the diagnosis of DED subclasses and therapeutic targets for DED patients.

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Section: Discussionmentioning

confidence: 99%

Tear Luminex Analysis in Dry Eye Patients

Zhao

et al. 2018

Med Sci Monit

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“…The multiplex assay analysis was performed according to a previously published protocol 25 . In brief, eppendorf tubes with tear and saliva samples were centrifuged (10 000 g for 10 min at 4 °C), one part of the supernatant was used for protein measurement, while an equal volume of PBS/1% bovine serum albumin (BSA) was added to the remaining sample.…”

Section: Methodsmentioning

confidence: 99%

Elevated cytokine levels in tears and saliva of patients with primary Sjögren’s syndrome correlate with clinical ocular and oral manifestations

Chen

Aqrawi

Utheim

et al. 2019

Sci Rep

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Investigating cytokines in tear fluid and saliva may offer valuable information for understanding the pathogenesis of primary Sjögren’s syndrome (pSS). Cytokine profiles in both tear fluid and saliva of pSS patients, non-Sjögren’s syndrome (non-SS) subjects with sicca symptoms, and healthy controls without sicca complaints were analysed. Furthermore, relationships associating the severity of clinical ocular and oral manifestations with the upregulated cytokines were assessed. In tear fluid, pSS patients showed elevated levels of IL-1ra, IL-2, IL-4, IL-8, IL-12p70, IL-17A, IFN-γ, IP-10, MIP-1b, and Rantes compared to non-SS subjects and healthy controls. The increased cytokine levels (except IP-10) correlated significantly with reduced tear production, less stable tear film, and greater ocular surface damage. In saliva, pSS patients had a higher IP-10 level, which correlated with higher candida score; and an elevated MIP-1a level, which correlated significantly with lower unstimulated and stimulated whole saliva secretion rates. The upregulated cytokines identified in tear fluid and saliva of pSS patients show a clear interplay between innate and adaptive immune responses that may contribute to disease pathogenesis. The increase of IP-10 and MIP in both tears and saliva further emphasises the essential role of macrophages and innate immunity in pSS.

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“…6 Furthermore, compared to healthy participants, the concentration of multiple proinflammatory Downloaded from iovs.arvojournals.org on 09/20/2020 mediators, such as IL-1β increased in the tear fluid, conjunctiva as well as eyelid margin of patients with MGD. [29][30][31] However, the role of inflammation in the pathophysiology of MGD is not entirely understood.…”

Section: Discussionmentioning

confidence: 99%

Organotypic Culture of Mouse Meibomian Gland: A Novel Model to Study Meibomian Gland Dysfunction In Vitro

Huang

Liu

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Meibomian glands are essential in maintaining the integrity and health of the ocular surface. Meibomian gland dysfunction (MGD), mainly induced by ductal occlusion, is considered as the major cause of dry eye disease. In this study, a novel in vitro model was established for investigating the role of inflammation in the process of MGD. METHODS. Mouse tarsal plates were removed from eyelids after dissection and explants were cultured during various time ranging from 24 to 120 hours. Meibomian gland epithelial cells were further enzymatically digested and dissociated from tarsal plates before culturing. Both explants and cells were incubated in different media with or without serum or azithromycin (AZM). Furthermore, explants were treated with IL-1β or vehicle for 48 hours. Analyses for tissue viability, histology, biomarker expression, and lipid accumulation were performed with hematoxylin and eosin (H&E) staining, immunofluorescence staining, and Western blot. RESULTS. Higher viability was preserved when explants were cultured on Matrigel with immediate addition of culture medium. The viability, morphology, biomarker expression, and function of meibomian glands were preserved in explants cultured for up to 72 hours. Lipid accumulation and peroxisome proliferator-activated receptor γ (PPARγ) expression increased in both explants and cells cultured in media containing serum or AZM. Treatment with IL-1β induced overexpression of Keratin (Krt) 1 in meibomian gland ducts. CONCLUSIONS. Intervention with pro-inflammatory cytokine IL-1β induces hyperkeratinization in meibomian gland ducts in vitro. This novel organotypic culture model can be used for investigating the mechanism of MGD.

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The Level of Inflammatory Tear Cytokines is Elevated in Congenital Aniridia and Associated with Meibomian Gland Dysfunction

Cited by 44 publications

References 32 publications

Tear Luminex Analysis in Dry Eye Patients

Tear Luminex Analysis in Dry Eye Patients

Elevated cytokine levels in tears and saliva of patients with primary Sjögren’s syndrome correlate with clinical ocular and oral manifestations

Organotypic Culture of Mouse Meibomian Gland: A Novel Model to Study Meibomian Gland Dysfunction In Vitro

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