Straube, Frank and Cirera Salinas, Daniel (2021) Membrane-tethered mucins and lubricin mediate the interfacial properties of model ocular epithelial surfaces. Advanced Science. ISSN 2198-38442198-3844

Abstract

The human ocular surface is enriched with endogenously expressed mucins, which are known to contribute to its lubricious character. Reduced biosynthesis or loss of functional mucins has been reported in some dry eye disease (DED) patients, contributing to mechanical alterations during blink cycles that can result in tissue damage and vision-threatening sequelae. While identifying strategies to reduce adhesion and shear stresses at the ocular surface is a promising approach to improve the signs and symptoms of DED, current pre-clinical models generally rely on scarce, heterogeneous tissue samples or model synthetic substrates that do not capture the complex biochemical and biophysical cues present at the ocular surface. Here we developed a mucin-deficient dry eye mimetic cell model and utilized contact angle hysteresis and step-strain rheological tests to investigate the contributions of mucins and mucin-like glycoproteins to the interfacial, rheological, and adhesive properties of ocular epithelial surfaces. This model system was designed with the purpose of providing mechanistic insight into the consequences of ocular surface mucin dysfunction that may inform treatment strategies. The contact angle hysteresis measurements showed that the hydration of the model ocular epithelial surfaces is maintained even in absence of endogenous membrane-tethered mucins. However, stress relaxation behaviors at the interface of model ocular surfaces demonstrated that membrane-tethered mucins are essential for biolubrication at the model interface. Supplementation with recombinant human lubricin, a mucin-like glycoprotein currently undergoing clinical trials for DED treatment, restored the lubrication function induced by the lack of cell surface mucins in a dose-dependent manner. This suggests that lubrication-related dysfunction due to mucin deficiency may be reversible and that recombinant human lubricin might be a promising treatment for DED patients. Together, these results demonstrate that mucin-deficient, biomimetic ocular surfaces serve as a promising platform for drug screening assays and fundamental studies of ocular surface biology.

Item Type:	Article
Date Deposited:	14 Jul 2021 00:45
Last Modified:	14 Jul 2021 00:45
URI:	https://oak.novartis.com/id/eprint/43588