Browse
Submit Data
Databases
API
Help

Dataset Information

26 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Membrane-associated mucins of the human ocular surface in health and disease.

ABSTRACT: Mucins are a family of high molecular weight, heavily-glycosylated proteins produced by wet epithelial tissues, including the ocular surface epithelia. Densely-packed O-linked glycan chains added post-translationally confer the biophysical properties of hydration, lubrication, anti-adhesion and repulsion. Membrane-associated mucins (MAMs) are the distinguishing components of the mucosal glycocalyx. At the ocular surface, MAMs maintain wetness, lubricate the blink, stabilize the tear film, and create a physical barrier to the outside world. In addition, it is increasingly appreciated that MAMs function as cell surface receptors that transduce information from the outside to the inside of the cell. Recently, our team published a comprehensive review/perspectives article for molecular scientists on ocular surface MAMs, including previously unpublished data and analyses on two new genes MUC21 and MUC22, as well as new MAM functions and biological roles, comparing human and mouse (PMID: 31493487). The current article is a refocus for the audience of The Ocular Surface. First, we update the gene and protein information in a more concise form, and include a new section on glycosylation. Next, we discuss biological roles, with some new sections and further updating from our previous review. Finally, we provide a new chapter on MAM involvement in ocular surface disease. We end this with discussion of an emerging mechanism responsible for damage to the epithelia and their mucosal glycocalyces: the unfolded protein response (UPR). The UPR offers a novel target for therapeutic intervention.

SUBMITTER: Martinez-Carrasco R

PROVIDER: S-EPMC8328898 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Membrane-associated mucins of the ocular surface: New genes, new protein functions and new biological roles in human and mouse.

Project description:The mucosal glycocalyx of the ocular surface constitutes the point of interaction between the tear film and the apical epithelial cells. Membrane-associated mucins (MAMs) are the defining molecules of the glycocalyx in all mucosal epithelia. Long recognized for their biophysical properties of hydration, lubrication, anti-adhesion and repulsion, MAMs maintain the wet ocular surface, lubricate the blink, stabilize the tear film and create a physical barrier to the outside world. However, it is increasingly appreciated that MAMs also function as cell surface receptors that transduce information from the outside to the inside of the cell. A number of excellent review articles have provided perspective on the field as it has progressed since 1987, when molecular cloning of the first MAM was reported. The current article provides an update for the ocular surface, placing it into the broad context of findings made in other organ systems, and including new genes, new protein functions and new biological roles. We discuss the epithelial tissue-equivalent with mucosal differentiation, the key model system making these advances possible. In addition, we make the first systematic comparison of MAMs in human and mouse, establishing the basis for using knockout mice for investigations with the complexity of an in vivo system. Lastly, we discuss findings from human genetics/genomics, which are providing clues to new MAM roles previously unimagined. Taken together, this information allows us to generate hypotheses for the next stage of investigation to expand our knowledge of MAM function in intracellular signaling and roles unique to the ocular surface.

| S-EPMC10276350 | biostudies-literature

Suppression of Toll-like receptor-mediated innate immune responses at the ocular surface by the membrane-associated mucins MUC1 and MUC16.

Project description:Membrane-associated mucins (MAMs) expressed on the ocular surface epithelium form a dense glycocalyx that is hypothesized to protect the cornea and conjunctiva from external insult. In this study, the hypothesis that the MAMs MUC1 and MUC16, expressed on the apical surface of the corneal epithelium, suppress Toll-like receptor (TLR)-mediated innate immune responses was tested. Using an in vitro model of corneal epithelial cells that are cultured to express MAMs, we show that reduced expression of either MUC1 or MUC16 correlates with increased message and secreted protein levels of the proinflammatory cytokines interleukin (IL)-6, IL-8, and tumor necrosis factor-α (TNF-α) following exposure of cells to the TLR2 and TLR5 agonists, heat-killed Listeria monocytogenes and flagellin, respectively. As mice express Muc1 (but not Muc16) in the corneal epithelium, a Muc1(-/-) mouse model was used to extend in vitro findings. Indeed, IL-6 and TNF-α message levels were increased in the corneal epithelium of Muc1(-/-) mice, in comparison with wild-type mice, following exposure of enucleated eyes to the TLR2 and TLR5 agonists. Our results suggest that the MAMs MUC1 and MUC16 contribute to the maintenance of immune homeostasis at the ocular surface by limiting TLR-mediated innate immune responses.

| S-EPMC4495011 | biostudies-literature

Thrombospondin-1 in ocular surface health and disease.

Project description:Thrombospondin 1 (TSP-1) is an extracellular matrix protein that interacts with a wide array of ligands including cell receptors, growth factors, cytokines and proteases to regulate various physiological and pathological processes. Constitutively expressed by certain ocular surface tissues (e.g. corneal and conjunctival epithelium), TSP-1 expression is modulated during ocular surface inflammation. TSP-1 is an important activator of latent TGF-β, serving to promote the immunomodulatory and wound healing functions of TGF-β. Mounting research has deepened our understanding of how TSP-1 expression (and lack thereof) contributes to ocular surface homeostasis and disease. Here, we review current knowledge of the function of TSP-1 in dry eye disease, ocular allergy, angiogenesis/lymphangiogenesis, corneal transplantation, corneal wound healing and infectious keratitis.

| S-EPMC6708501 | biostudies-literature

Accelerated Restoration of Ocular Surface Health in Dry Eye Disease by Self-Retained Cryopreserved Amniotic Membrane.

Project description:To evaluate the clinical efficacy of self-retained cryopreserved amniotic membrane in treating dry eye disease.Retrospective review of 10 patients treated with self-retained cryopreserved amniotic membrane (PROKERA® Slim [PKS], Bio-Tissue, Miami, FL) for moderate-to-severe dry eye refractory to conventional maximal medical treatments. Patients' symptoms, use of medications, conjunctival inflammation, corneal staining, and visual acuity were compared before and after treatment.PKS was placed in 15 eyes of the 10 patients for 4.9 ± 1.5 days. All patients experienced symptomatic relief for a period of 4.2 ± 4.7 months (P<.001). Such improvement was accompanied by reduction of OSDI scores (P<.001), use of topical medications (P<.001), conjunctival hyperemia (P<.001), corneal staining (P<.001), and improvement of the visual acuity (P=.06). Linear regression analysis estimated that the optimal duration of PKS placement was 5 days to achieve an average symptom-free duration of 4 months in patients with dry eye. Surprisingly, PKS placement also generated improvement in the contralateral eyes.This pilot study suggests that self-retained cryopreserved amniotic membrane via PKS can be used to treat moderate dry eye diseases and warrants further prospective controlled studies.

| S-EPMC4706470 | biostudies-literature

Urea-De-Epithelialized Human Amniotic Membrane for Ocular Surface Reconstruction.

Project description:The conjunctiva is a clear tissue covering the white part of the eye and lines the back of the eyelids. Conjunctival diseases, such as symblepharon, cause inflammation, discharges, and photophobia. The treatment often requires excision of large parts of conjunctiva. Tissue engineering of conjunctival cells using human amniotic membrane (HAM) denuded of its epithelium as a basement membrane scaffold has been shown to be effective for covering conjunctival defects. However, most epithelial denudation protocols are time-consuming and expensive or compromise HAM's basement membrane structure and matrix components. We have previously described a method to de-epithelialize HAM using ice-cold urea (uHAM). In this report, we used this method to provide tissue-engineered constructs with cultivated conjunctival epithelial cells on uHAM in two patients, one with a giant conjunctival nevus and the other with a large symblepharon. Autologous conjunctival epithelial cells harvested from incisional biopsies of these two patients were cultured on the uHAM scaffold. The transplantation of tissue-engineered constructs to patients' ocular surface immediately after the removal of lesions showed successful reconstruction of the ocular surface. Postoperatively, there were neither recurrence of lesions nor epithelial defects throughout the follow-up (up to 7 and 19 months, respectively). This report highlights the translational potential of an efficient and inexpensive method to prepare de-epithelialized HAM as a basement membrane scaffold for cell-based tissue-engineered treatments of ocular surface disorders. Stem Cells Translational Medicine 2019;8:620&626.

| S-EPMC6591546 | biostudies-literature

Lacritin and other autophagy associated proteins in ocular surface health.

Project description:Advantage may be taken of macroautophagy ('autophagy') to promote ocular health. Autophagy continually captures aged or damaged cellular material for lysosomal degradation and recyling. When autophagic flux is chronically elevated, or alternatively deficient, health suffers. Chronic elevation of flux and stress are the consequence of inflammatory cytokines or of dry eye tears but not normal tears invitro. Exogenous tear protein lacritin transiently accelerates flux to restore homeostasis invitro and corneal health invivo, and yet the monomeric active form of lacritin appears to be selectively deficient in dry eye. Tissue transglutaminase-dependent cross-linking of monomer decreases monomer quantity and monomer affinity for coreceptor syndecan-1 thereby abrogating activity. Tissue transglutaminase is elevated in dry eye. Mutation of arylsulfatase A, arylsulfatase B, ceroid-lipofuscinosis neuronal 3, mucolipin, or Niemann-Pick disease type C1 respectively underlie several diseases of apparently insufficient autophagic flux that affect the eye, including: metachromatic leukodystrophy, mucopolysaccharidosis type VI, juvenile-onset Batten disease, mucolipidosis IV, and Niemann-Pick type C associated with myelin sheath destruction of corneal sensory and ciliary nerves and of the optic nerve; corneal clouding, ocular hypertension, glaucoma and optic nerve atrophy; accumulation of 'ceroid-lipofuscin' in surface conjunctival cells, and in ganglion and neuronal cells; decreased visual acuity and retinal dystrophy; and neurodegeneration. For some, enzyme or gene replacement, or substrate reduction, therapy is proving to be successful. Here we discuss examples of restoring ocular surface homeostasis through alteration of autophagy, with particular attention to lacritin.

| S-EPMC4698016 | biostudies-literature

Trehalose for Ocular Surface Health.

Project description:Trehalose is a natural disaccharide synthesized in various life forms, but not found in vertebrates. An increasing body of evidence demonstrates exceptional bioprotective characteristics of trehalose. This review discusses the scientific findings on potential functions of trehalose in oxidative stress, protein clearance, and inflammation, with an emphasis on animal models and clinical trials in ophthalmology. The main objective is to help understand the beneficial effects of trehalose in clinical trials and practice, especially in patients suffering from ocular surface disease. The discussion is supplemented with an overview of patents for the use of trehalose in dry eye and with prospects for the 2020s.

| S-EPMC7277924 | biostudies-literature

Ocular Surface Potential Difference Measured in Human Subjects to Study Ocular Surface Ion Transport.

Project description:PurposeThe epithelium lining the ocular surface, which includes corneal and conjunctival epithelia, expresses the prosecretory chloride channel cystic fibrosis transmembrane conductance regulator (CFTR) and the proabsorptive epithelial sodium channel (ENaC). Here, methodology was established to measure the millivolt (mV) potential differences at the ocular surface, called ocular surface potential difference (OSPD), in human subjects produced by ion transport.MethodsOSPD was measured in human subjects in which a fluid-filled measuring electrode contacted a fluid pool created by eversion of the lateral lower eyelid, with a reference electrode placed subcutaneously in the forearm. Through the use of a high-impedance voltmeter, OSPD was measured continuously over 10 to 15 minutes in response to a series of perfusate fluid exchanges.ResultsBaseline OSPD (± SEM) in six normal human subjects was -21.3 ± 3.6 mV. OSPD depolarized by 1.7 ± 0.6 mV following the addition of the ENaC inhibitor amiloride, hyperpolarized by 6.8 ± 1.5 mV with a zero chloride solution, and further hyperpolarized by 15.9 ± 1.6 mV following CFTR activation by isoproterenol. The isoproterenol-induced hyperpolarization was absent in two cystic fibrosis subjects lacking functional CFTR. OSPD measurement produced minimal epithelial injury.ConclusionsOur results establish the feasibility and safety of OSPD measurement in humans and demonstrate robust CFTR activity, albeit minimal ENaC activity, at the ocular surface. OSPD measurement may be broadly applicable to investigate fluid transport mechanisms and test drug candidates to treat ocular surface disorders.Translational relevanceTo the best of our knowledge, this is the first measurement of the electrical potential generated by the ocular surface epithelium in human subjects, offering a new approach to study ocular surface function and health.

| S-EPMC7571274 | biostudies-literature

Mouse and Human Conjunctiva Organoids to Study Ocular Surface Homeostasis and Disease

Project description:The conjunctival epithelium covering the eye consists of two main differentiated cell types: mucus-producing Goblet cells and ‘keratinocytes’ of unknown function. Here, we describe long-term expanding organoids representing human conjunctiva. To check if interleukins may boost secretome expression, we stimulated the organoid cells with pleiotropic anti-inflammatory cytokines interleukin-4 and IL-13. Secretions were identified by shotgun MS to quantitatively enriched secreted proteins.

2024-01-11 | PXD043550 | Pride

Sutureless fixation of amniotic membrane for therapy of ocular surface disorders.

Project description:Amniotic membrane is applied to the diseased ocular surface to stimulate wound healing and tissue repair, because it releases supportive growth factors and cytokines. These effects fade within about a week after application, necessitating repeated application. Generally, amniotic membrane is fixed with sutures to the ocular surface, but surgical intervention at the inflamed or diseased site can be detrimental. Therefore, we have developed a system for the mounting of amniotic membrane between two rings for application to a diseased ocular surface without surgical intervention (sutureless amniotic membrane transplantation). With this system, AmnioClip, amniotic membrane can be applied like a large contact lens. First prototypes were tested in an experiment on oneself for wearing comfort. The final system was tested on 7 patients in a pilot study. A possible influence of the ring system on the biological effects of amniotic membrane was analyzed by histochemistry and by analyzing the expression of vascular endothelial growth factor-A (VEGF-A), hepatocyte growth factor (HGF), fibroblast growth factor 2 (FGF 2) and pigment epithelium-derived factor (PEDF) from amniotic membranes before and after therapeutic application. The final product, AmnioClip, showed good tolerance and did not impair the biological effects of amniotic membrane. VEGF-A and PEDF mRNA was expressed in amniotic membrane after storage and mounting before transplantation, but was undetectable after a 7-day application period. Consequently, transplantation of amniotic membranes with AmnioClip provides a sutureless and hence improved therapeutic strategy for corneal surface disorders.Trial Registration:ClinicalTrials.gov NCT02168790

| S-EPMC4425509 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data