Interaction of phospholipid transfer protein with human tear fluid mucins

Abstract

This article is available online at http://www.jlr.org well as an economic burden to patients and the community. DES is considered to arise from the interplay of inadequate tear production, increased tear evaporation, and altered composition of the tear fi lm. The underlying biochemical and physiological events in the development of DES and precise composition of the human tear fl uid are only partially understood. Until now the model of the tear fi lm has been a three-layered structure ( 2, 3 ): the inner mucin-enriched phase and the middle aqueous layer with soluble proteins form a gel-like structure while the outermost layer consists of lipids. On the basis of analysis of meibomian gland secretions, the lipid layer is suggested to be composed of wax esters, sterol esters, and polar lipids ( 4, 5 ). It has been suggested, based on the hydrophobic effect, that the charged (polar) phospholipids are disposed adjacent to the aqueous-mucin layer and, externally to this, a layer composed of nonpolar lipids, such as cholesteryl esters and triglycerides, face the tear-air interface (6)(7)(8). This type of lipid organization is believed to strongly oppose evaporation. Yet, the ocular and mucin components become vulnerable to lipid contamination, which would lead to dewetting of the corneal epithelium. A mechanism to organize and maintain homeostasis of the lipid layer and to prevent epithelial or mucin contamination is needed. Indeed, lipocalin, one such kind of protein, has been confi rmed to effi ciently remove lipids from the corneal surface ( 9 ). Yet this observation does not ex- Dry eye syndrome (DES), the most common ocular disorder that affects around 14% of individuals aged 65 ± 10 years ( 1 ), poses a considerable public health problem as Abbreviations: Apo, apolipoprotein; BSM, bovine submaxillary gland mucin; CETP, cholesteryl ester transfer protein; DES, dry eye syndrome; H-S, heparin-sepharose; MUC, mucin; OVM, ovomucin; PLTP, phospholipid transfer protein; SEC, size exclusion chromatography; Tlc, human tear lipocalin.

TFOS DEWS II Tear Film Report

“…Secreted mucins may have an active role in lipid organization at the surface of the tear film [296,509] and phospholipid transfer protein functions to scavenge lipophilic substances from ocular mucins [510], but data supporting a direct interaction between mucins and lipids are lacking. In the epithelial glycocalyx, the transmembrane mucins MUC1 and MUC16 bind galectin-3 to promote ocular surface barrier function [382].…”

Practical issues concerning tear protein assays in dry eye

“…Understanding of tear mucin regulation may produce insight into the mechanism of at least some types of dry eye [ 49 ]. Phospholipid transfer protein, a protein that interacts with mucins, may also be relevant to the dry eye mechanism [ 104 ], but this has not been studied well enough to be used for clinical purposes. Since the regulation of mucin affects dry eye pathologic mechanisms, it gives greater credibility to the use of mucins as a marker for this disease.…”

Lipidomic analysis of human tear fluid reveals structure-specific lipid alterations in dry eye syndrome

“…enhanced levels of these lipids. It has been shown that both lipocalin ( 29 ) and phospholipid transfer protein ( 30 ) in human tears serve to scavenge lipids from corneal surfaces to ensure a "wettable" cornea. Specifi cally, it was stated that phospholipid transfer protein knockout mice developed appreciable DES and elevated corneal epithelial permeability ( 30 ), which is also in accordance with the accumulation of phospholipids in DES observed in our study.…”