Human ocular mucins: The endowed guardians of sight

Abstract

Mucins are an ancient group of glycoproteins that provide viscoelastic, lubricating and hydration properties to fluids bathing wet surfaced epithelia. They are involved in the protection of underlying tissues by forming a barrier with selective permeability properties. The expression, processing and spatial distribution of mucins are often determined by organ-specific requirements that in the eye involve protecting against environmental insult while allowing the passage of light. The human ocular surface epithelia have evolved to produce an extremely thin and watery tear film containing a distinct soluble mucin product secreted by goblet cells outside the visual axis. The adaptation to the ocular environment is notably evidenced by the significant contribution of transmembrane mucins to the tear film, where they can occupy up to one-quarter of its total thickness. This article reviews the tissue-specific properties of human ocular mucins, methods of isolation and detection, and current approaches to model mucin systems recapitulating the human ocular surface mucosa. This knowledge forms the fundamental basis to develop applications with a promising biological and clinical impact.

Keywords: Epithelium; Goblet cell; Mucin; Ocular surface; Tear film.

Fig. 1.

Schematic representation of normal epithelia from the human ocular surface, airway and colon. The morphological appearance is closely associated to the tissue-specific requirements of each mucosal surface. The tear film is an extremely thin and watery fluid that functions as the primary refracting surface of the eye. The airway mucosa prevents desiccation and facilitates the removal of inhaled debris and pathogens through mucociliary transport. It comprises an apical layer of gel-forming mucins and a periciliary layer that facilitates ciliary beating and fluid flow. The colon has an inner layer of mucus that is attached to the epithelium and an outer layer that is less dense and serves as the habitat for commensal bacteria. Gel-forming mucins are shown in blue and transmembrane mucins in green.

Fig. 2.

Structure and tissue-specific properties of MUC5AC at the ocular surface. A. Relative topographic distribution of goblet cells (blue dots) in the human conjunctiva (adapted from [161]). B. Schematic representation of the structure of MUC5AC containing three vWF type D domains (D1-D3) and a truncated D domain (D’) at the N-terminus, and a cystine-knot (CK) domain and a fourth vWF type D domain (D4) at the C-terminus. The central mucin domain is composed of repetitive and non-repetitive sequences enriched in proline, threonine and serine interspersed with CYS domains (in yellow). The mucin undergoes disulfide-mediated dimerization in the endoplasmic reticulum, matures and multimerizes via the N-terminal D domains in the Golgi apparatus, and is finally secreted as a polymeric network into the extracellular fluid where it forms an entangled hydrogel. C. MUC5AC in the tear fluid has a higher electrophoretic mobility compared to intracellular MUC5AC present in conjunctiva or other mucosal surfaces such as fundus, gall bladder and cervix (adapted from [50]).