Release of Membrane-Associated Mucins from Ocular Surface Epithelia

Blalock, Timothy D.; Spurr-Michaud, Sandra; Tisdale, Ann; Gipson, Ilene K.

doi:10.1167/iovs.07-1081

Cited by 96 publications

(80 citation statements)

References 40 publications

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“…39,52 MMP-7 has been reported to cleave MUC16, the principal mucin constituent of the cornea epithelial glycocalyx, from cultured human cornea epithelial cell membranes. 40 Taken together, these findings implicate MMPs in the disruption of molecules maintaining para-and transcellular cornea barrier.…”

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confidence: 81%

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Matrix metalloproteinase-9 in the pathophysiology and diagnosis of dry eye syndrome

Pflugfelder¹,

Bian²,

Paiva³

2017

MNM

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Dry eye and tear dysfunction are common ocular disorders that cause cornea barrier disruption resulting in a poorly lubricated and irregular cornea epithelium, eye irritation and blurred vision. Increased levels and activities of matrix metalloproteinases (MMPs), particularly MMP-9, have been detected in the tears and ocular surface epithelial and inflammatory cells in dry eye. MMPs have been found to participate in disruption of tight junctions in the apical cornea epithelium leading to their accelerated desquamation and barrier disruption. This review summarizes evidence showing the contribution of MMPs to dry eye pathogenesis and their roles as biomarkers and therapeutic targets. Keywords: matrix metalloproteinase, dry eye, keratitis sicca, cornea, barrier function, Sjögren syndrome Dry eye overviewDry eye and tear dysfunction are common ocular disorders that cause cornea barrier disruption resulting in a poorly lubricated and irregular cornea epithelium, eye irritation and blurred vision. It affects millions of people worldwide and is one of the most frequent conditions for which patients seek eye care.1 Aging and female sex are significant risk factors for dry eye which increases in prevalence around the fifth decade, with further increase every decade thereafter.2-13 Prevalence of dry eye varies from 2% to 50%, depending on the population studied and the diagnostic criteria for dry eye (symptom questionnaire vs. objective signs). [1][2][3]6,7,[9][10][11][14][15][16][17][18][19][20][21][22][23] There is scarce information about the natural history of dry eye, but there is a recognized disconnection between signs and symptoms; patients tend to be more symptomatic at early stages.24,25 Dry eye causes corneal irregularity [26][27][28] and decreases functional vision by altering contrast sensitivity [29][30][31] and, therefore, decreases quality of life with a significant burden on the individual as well as the society. 23,[32][33][34][35] A meta-analysis of 22 published studies showed increased odds ratio for depression and anxiety in patients with ocular Sjögren syndrome (SS). 36 There is increased evidence that dry eye is an inflammatory disease, and this review will focus on matrix metalloproteinases (MMPs) and their role in the pathogenesis of dry eye. Cornea barrier disruption is a feature of dry eyeAs the principal lens of the eye, the cornea has unique features to maintain its transparency and smooth surface that include a lack of blood vessels and a multilayered stratified, non-cornifying epithelium. The differentiated apical epithelial cells produce

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confidence: 81%

“…[38][39][40] Gelatinases have been implicated in physiologic desquamation of the cornea epithelium. Decreased corneal epithelial desquamation in vitamin A-deficient rats was associated with significantly decreased MMP-2 and -9 expression.…”

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confidence: 99%

Matrix metalloproteinase-9 in the pathophysiology and diagnosis of dry eye syndrome

Pflugfelder¹,

Bian²,

Paiva³

2017

MNM

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“…The triggers and mechanisms involved in release of the ectodomain are only partially understood. It has been hypothesized that mucin extracellular domains are released in response to mechanical force, interactions with microbes or alteration in pH, ionic concentration, hydration [4] or inflammatory stimuli such as TNFα and neutrophil elastase [29]. At the mucosal surface, the shed domains might function as decoy receptors for pathogens.…”

Section: General Features Of Transmembrane Mucinsmentioning

confidence: 99%

Transmembrane Mucins: Signaling Receptors at the Intersection of Inflammation and Cancer

Putten¹,

Strijbis²

2017

J Innate Immun

206

213

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Mucosal surfaces line our body cavities and provide the interaction surface between commensal and pathogenic microbiota and the host. The barrier function of the mucosal layer is largely maintained by gel-forming mucin proteins that are secreted by goblet cells. In addition, mucosal epithelial cells express cell-bound mucins that have both barrier and signaling functions. The family of transmembrane mucins consists of diverse members that share a few characteristics. The highly glycosylated extracellular mucin domains inhibit invasion by pathogenic bacteria and can form a tight mesh structure that protects cells in harmful conditions. The intracellular tails of transmembrane mucins can be phosphorylated and connect to signaling pathways that regulate inflammation, cell-cell interactions, differentiation, and apoptosis. Transmembrane mucins play important roles in preventing infection at mucosal surfaces, but are also renowned for their contributions to the development, progression, and metastasis of adenocarcinomas. In general, transmembrane mucins seem to have evolved to monitor and repair damaged epithelia, but these functions can be highjacked by cancer cells to yield a survival advantage. This review presents an overview of the current knowledge of the functions of transmembrane mucins in inflammatory processes and carcinogenesis in order to better understand the diverse functions of these multifunctional proteins.

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“…MUC16 can be cleaved between the N-and C-terminal fragments, possibly in the SEA (sea urchin sperm protein, enterokinase, and agrin) domain, with potential influence on immunoreactivity, since both epitopes for OC125 and M11-like antibodies contain parts of two consecutive SEA domains with a linker (Maeda et al, 2004;Blalock et al, 2008). So far, proteomic profiling identified a 2351.2 kDa protein/spot as high molecular mass MUC16/CA125 (Milardi et al, 2012), but a CA125-immunoreactive band at 130 kDa was also observed in another immunoblot study (Halila, 1985).…”

Section: Discussionmentioning

confidence: 99%

Analysis of CA125 antigen in normal human seminal plasma highlightsthe molecular heterogeneity of underlying glycosylated species

Mitić¹,

Milutinović²,

Janković³

2017

Turk J Biol

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led to its definition as a repeating peptide epitope on MUC16 (Yin et al., 2001). The epitope map of CA125 is, however, very complex and varies among mucin molecules expressed under different pathophysiological conditions and from different sources. This results in typical/unique patterns sharing some commonality (Nustad et al., 2002).Structural data obtained on CA125/MUC16 indicated extreme heterogeneity, probably due to the existence of molecular species differing in mass and glycosylation. CA125-immunoreactivity was associated with high molecular mass macromolecular moieties of 3-5 MDa mucin and 400 kDa-200 kDa precursors, but also with low molecular mass species at 55 and 40, down to 10-15 kDa (Hanisch et al., 1985;Nustad et al., 1998;Yin et al., 2001). As for glycosylation, the total glycan content varied from moderate, as in glycoproteins, to extremely high (more than 28%), as in mucins (Kui Wong et al., 2003). Relatively high abundance of N-glycans, not typical for other mucins and diverse O-glycan associated epitopes such as CA19-9 and sTn, have been reported (

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Release of Membrane-Associated Mucins from Ocular Surface Epithelia

Abstract: Results suggest that the extracellular domains of MUC1, MUC4, and MUC16 can be released from the ocular surface by agents in tears. Neutrophil elastase and TNF, present in higher amounts in the tears of patients with dry eye, may cause MAM release, allowing rose bengal staining.

Cited by 96 publications

References 40 publications

Matrix metalloproteinase-9 in the pathophysiology and diagnosis of dry eye syndrome

Matrix metalloproteinase-9 in the pathophysiology and diagnosis of dry eye syndrome

Transmembrane Mucins: Signaling Receptors at the Intersection of Inflammation and Cancer

Analysis of CA125 antigen in normal human seminal plasma highlightsthe molecular heterogeneity of underlying glycosylated species

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