Understanding the adsorption and potential tear film stability properties of recombinant human lubricin and bovine submaxillary mucins in an in vitro tear film model

Rabiah, Noelle I.; Sato, Yasunori; Kannan, Aadithya; Kress, Wolfgang; Sträube, Frank; Fuller, Gerald G.

doi:10.1016/j.colsurfb.2020.111257

Cited by 17 publications

(25 citation statements)

References 42 publications

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“…In many scenarios involving foam and emulsion films, it is necessary to measure the film thickness at both high temporal and spatial resolutions. This has motivated a number of researchers to perform studies with custom built thin film interferometry apparatuses [8,9,17,39,42,43,67,70,78,80,[101][102][103][104][105][106][107][108][109][110][111][112][113][114][115].…”

Section: Thin Film Profile Reconstructionmentioning

confidence: 99%

Single bubble and drop techniques for characterizing foams and emulsions

Suja

Rodríguez-Hakim

Tajuelo

et al. 2020

Advances in Colloid and Interface Science

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Section: Thin Film Profile Reconstructionmentioning

confidence: 99%

Single bubble and drop techniques for characterizing foams and emulsions

Suja

Rodríguez-Hakim

Tajuelo

et al. 2020

Advances in Colloid and Interface Science

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“…Proteoglycan 4 (PRG4), also known as lubricin, is a mucin-like glycoprotein with an important role in maintaining homeostasis through its ability to provide boundary lubrication and regulate inflammatory signaling ( Das et al, 2019 ). PRG4 expression in the eye is found to be critical for ocular surface composition ( Schmidt et al, 2013 ; Samsom et al, 2015 ) and maintaining tear film integrity ( Rabiah et al, 2020 ), as evidenced by the Prg4 −/− mice that displayed significantly higher red corneal fluorescein staining (representing damage of the ocular surface) compared to wild type counterparts ( Schmidt et al, 2013 ). A recent clinical trial showed that recombinant human PRG4 (rhPRG4) was effective at reducing signs and symptoms of dry eye disease, where ∼38% of the people enrolled were SS patients ( Lambiase et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Proteomics Analysis of Tears and Saliva From Sjogren’s Syndrome Patients

et al. 2021

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Sjogren’s syndrome (SS) is characterized by dysfunctional mucous membranes and dysregulated moisture-secreting glands resulting in various symptoms, including dry mouth and dry eyes. Here, we wanted to profile and compare the tear and saliva proteomes of SS patients to healthy controls. Tear and saliva samples were collected and subjected to an isotopic dimethylation labeling shotgun proteomics workflow to identify alterations in protein levels. In tear samples, we identified 83 upregulated and 112 downregulated proteins. Pathway enrichment analysis of the changing proteins by Metascape identified leukocyte transendothelial migration, neutrophil degranulation, and post-translation protein phosphorylation in tears of SS patients. In healthy controls’ tears, an enrichment for proteins related to glycolysis, amino acid metabolism and apoptotic signaling pathway were identified. In saliva, we identified 108 upregulated and 45 downregulated proteins. Altered pathways in SS patients’ saliva included cornification, sensory perception to taste and neutrophil degranulation. In healthy controls’ saliva, an enrichment for proteins related to JAK-STAT signaling after interleukin-12 stimulation, phagocytosis and glycolysis in senescence were identified. Dysregulated protease activity is implicated in the initiation of inflammation and immune cell recruitment in SS. We identified 20 proteases and protease inhibitors in tears and 18 in saliva which are differentially expressed between SS patients and healthy controls. Next, we quantified endogenous proteoglycan 4 (PRG4), a mucin-like glycoprotein, in tear wash and saliva samples via a bead-based immune assay. We identified decreased levels of PRG4 in SS patients’ tear wash compared to normal samples. Conversely, in saliva, we found elevated levels of PRG4 concentration and visualized PRG4 expression in human parotid gland via immunohistological staining. These findings will improve our mechanistic understanding of the disease and changes in SS patients’ protein expression will help identify new potential drug targets. PRG4 is among the promising targets, which we identified here, in saliva, for the first time.

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“…[ 16 , 38 ] Additionally, DLS measurement showed that the hydrodynamic diameter of purified rh‐lubricin was 65.4 ± 1.1 nm (Figure S5C , Supporting Information), consistent with previous reports. [ 39 ] A lectin blot using FITC‐Jacalin also confirmed the presence of O‐glycans on purified rh‐lubricin (Figure S5B , Supporting Information). Moreover, purified rh‐lubricin possesses sialic acid residues, as shown by the downward shift in the molecular weight following sialidase treatment.…”

Section: Resultsmentioning

confidence: 77%

Mucin‐Like Glycoproteins Modulate Interfacial Properties of a Mimetic Ocular Epithelial Surface

et al. 2021

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Dry eye disease (DED) has high personal and societal costs, but its pathology remains elusive due to intertwined biophysical and biochemical processes at the ocular surface. Specifically, mucin deficiency is reported in a subset of DED patients, but its effects on ocular interfacial properties remain unclear. Herein a novel in vitro mucin‐deficient mimetic ocular surface (Mu‐DeMOS) with a controllable amount of membrane‐tethered mucin molecules is developed to represent the diseased ocular surfaces. Contact angle goniometry on mimetic ocular surfaces reveals that high surface roughness, but not the presence of hydrophilic mucin molecules, delivers constant hydration over native ocular surface epithelia. Live‐cell rheometry confirms that the presence of mucin‐like glycoproteins on ocular epithelial cells reduces shear adhesive strength at cellular interfaces. Together, optimal surface roughness and surface chemistry facilitate sustainable lubrication for healthy ocular surfaces, while an imbalance between them contributes to lubrication‐related dysfunction at diseased ocular epithelial surfaces. Furthermore, the restoration of low adhesive strength at Mu‐DeMOS interfaces through a mucin‐like glycoprotein, recombinant human lubricin, suggests that increased frictional damage at mucin‐deficient cellular surfaces may be reversible. More broadly, these results demonstrate that Mu‐DeMOS is a promising platform for drug screening assays and fundamental studies on ocular physiology.

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Understanding the adsorption and potential tear film stability properties of recombinant human lubricin and bovine submaxillary mucins in an in vitro tear film model

Cited by 17 publications

References 42 publications

Single bubble and drop techniques for characterizing foams and emulsions

Single bubble and drop techniques for characterizing foams and emulsions

Proteomics Analysis of Tears and Saliva From Sjogren’s Syndrome Patients

Mucin‐Like Glycoproteins Modulate Interfacial Properties of a Mimetic Ocular Epithelial Surface

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