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

Fini, M. Elizabeth; Jeong, Shinwu; Gong, Haiyan; Martínez-Carrasco, Rafael; Laver, Nora; Hijikata, Makoto; Keicho, Naoto; Argüeso, Pablo

doi:10.1016/j.preteyeres.2019.100777

Cited by 37 publications

(44 citation statements)

References 284 publications

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“…17,27 Membrane-associated mucins are lower in molecular weight, with the extracellular domain spanning 200-500 nm and a short cytoplasmic tail anchored into the cellular surface. 28,29 In both secreted and membrane-associated mucins, the ''core'' section of the polypeptide backbone comprises PTS domains and is densely grafted via O-linkage at the threonine and serine residues with oligosaccharides (O-glycosylated). These side chains contain 2-22 sugar units and can be can linear or moderately branched, conferring mucins with a brush-like structure.…”

Section: Mucus and Mucinsmentioning

confidence: 99%

“…22,[32][33][34][35] Similar to mucus in other organs, ocular mucus serves many important physiological functions, including hydration, lubrication, cell signaling, and protection of the underlying epithelia from external noxious agents. 15,[22][23][24]28,29,36 Two types of secreted mucins are present at the ocular surface: large gel-forming mucins (MUC2, MUC5AC, MUC5B, and MUC6) and smaller soluble mucins (MUC7 and MUC9). 22,28,29,35,36 They are produced predominantly by goblet cells in the conjunctiva epithelium and released into the tear film.…”

Section: Ocular Mucusmentioning

confidence: 99%

“…15,[22][23][24]28,29,36 Two types of secreted mucins are present at the ocular surface: large gel-forming mucins (MUC2, MUC5AC, MUC5B, and MUC6) and smaller soluble mucins (MUC7 and MUC9). 22,28,29,35,36 They are produced predominantly by goblet cells in the conjunctiva epithelium and released into the tear film. MUC5AC is the most prevalent secreted ocular mucin; it is present in healthy tear fluid at concentrations as high as 200 mg/mL (MUC2, MUC5B, MUC6, MUC7, and MUC9 are secreted at levels that are orders of magnitude lower).…”

Section: Ocular Mucusmentioning

confidence: 99%

“… 17 , 27 Membrane-associated mucins are lower in molecular weight, with the extracellular domain spanning 200–500 nm and a short cytoplasmic tail anchored into the cellular surface. 28 , 29 …”

Section: Mucus and Mucinsmentioning

confidence: 99%

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Mucus-Penetrating Particles and the Role of Ocular Mucus as a Barrier to Micro- and Nanosuspensions

Попов

2020

Journal of Ocular Pharmacology and Therapeutics

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The ocular surface is naturally covered with a layer of mucus. Along with other functions, this mucus layer serves to trap and eliminate foreign substances, such as allergens, pathogens, and debris. In playing this pivotal role, mucus can also hinder topical delivery of therapeutics to the eye. Recent studies provide evidence that drugs formulated as traditional micro-or nanoparticles are susceptible to entrapment and rapid clearance by ocular mucus. Mucus-penetrating particles (MPPs) is a nanoparticle technology that emerged over the past decade. With a muco-inert surface and a particle size smaller than the mucus mesh size, MPPs can diffuse in ex vivo mucus essentially freely. Preclinical studies have shown that, compared with particles lacking the mucus-penetrating attributes, MPPs can improve the uniformity of drug particle distribution on mucosal surfaces and enhance drug delivery to ocular tissues.

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Section: Mucus and Mucinsmentioning

confidence: 99%

Section: Ocular Mucusmentioning

confidence: 99%

Section: Ocular Mucusmentioning

confidence: 99%

Section: Mucus and Mucinsmentioning

confidence: 99%

See 2 more Smart Citations

Mucus-Penetrating Particles and the Role of Ocular Mucus as a Barrier to Micro- and Nanosuspensions

Попов

2020

Journal of Ocular Pharmacology and Therapeutics

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“…The glycocalyx mainly consists of membrane bound mucins. It is covered by a mucoaqueous tear layer with lubricating properties predominantly due to dissolved gel-forming mucin MUC5AC secreted by conjunctival goblet cells [21][22][23][24][25][26][27][28][29]. The glycoprotein MUC5AC consists of a long protein molecule with oligosaccharide side chains linked by O-glycosylation to the protein backbone [23,30].…”

Section: Ocular Surface Homeostasismentioning

confidence: 99%

Why Chain Length of Hyaluronan in Eye Drops Matters

Müller-Lierheim¹

2020

Diagnostics

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The chain length of hyaluronan (HA) determines its physical as well as its physiological properties. Results of clinical research on HA eye drops are not comparable without this parameter. In this article methods for the assessment of the average molecular weight of HA in eye drops and a terminology for molecular weight ranges are proposed. The classification of HA eye drops according to their zero shear viscosity and viscosity at 1000 s−1 shear rate is presented. Based on the gradient of mucin MUC5AC concentration within the mucoaqueous layer of the tear film a hypothesis on the consequences of this gradient on the rheological properties of the tear film is provided. The mucoadhesive properties of HA and their dependence on chain length are explained. The ability of HA to bind to receptors on the ocular epithelial cells, and in particular the potential consequences of the interaction between HA and the receptor HARE, responsible for HA endocytosis by corneal epithelial cells is discussed. The physiological function of HA in the framework of ocular surface homeostasis and wound healing are outlined, and the influence of the chain length of HA on the clinical performance of HA eye drops is illustrated. The use of very high molecular weight HA (hylan A) eye drops as drug vehicle for the next generation of ophthalmic drugs with minimized side effects is proposed and its advantages elucidated. Consequences of the diagnosis and treatment of ocular surface disease are discussed.

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The Role of Membrane‐Tethered Mucins in Axial Epithelial Adhesion in Controlled Normal Stress Environments

Baumli,

Liu,

Bekčić

et al. 2023

Advanced Biology

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The collective adhesive behavior of epithelial cell layers mediated by complex macromolecular fluid environments plays a vital role in many biological processes. Mucins, a family of highly glycosylated proteins, are known to lubricate cell‐on‐cell contacts in the shear direction. However, the role of mucins mediating axial epithelial adhesion in the direction perpendicular to the plane of the cell sheet has received less attention. This article subjects cell‐on‐cell layers of live ocular epithelia that express mucins on their apical surfaces to compression/decompression cycles and tensile loading using a customized instrument. In addition to providing compressive moduli of native cell‐on‐cell layers, it is found that the mucin layer between the epithelia acts as a soft cushion between the epithelial cell layers. Decompression experiments reveal mucin layers act as soft, nonlinear springs in the axial direction. The cell‐on‐cell layers withstand decompression before fracturing by a cohesive failure within the mucin layer. When mucin deficiency is induced via a protease treatment, it is found that the axial adhesion between the cell layers is increased. The findings which correlate changes in biological factors with changes in mechanical properties might be of interest to challenges in ophthalmology, vision care, and mucus research.

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

Cited by 37 publications

References 284 publications

Mucus-Penetrating Particles and the Role of Ocular Mucus as a Barrier to Micro- and Nanosuspensions

Mucus-Penetrating Particles and the Role of Ocular Mucus as a Barrier to Micro- and Nanosuspensions

Why Chain Length of Hyaluronan in Eye Drops Matters

The Role of Membrane‐Tethered Mucins in Axial Epithelial Adhesion in Controlled Normal Stress Environments

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