E-Cadherin Is Important for Meibomian Gland Function as Revealed by a New Human ex Vivo Slice Culture Model

Abstract

Meibomian glands within the eyelid are important for the maintenance of the integrity and health of the ocular surface. Patients with the blistering skin disease pemphigus vulgaris (PV), which is caused by autoantibodies against desmosomal cadherins, often have dry eye disease. Therefore, we studied the regulation of cell cohesion in human meibomian gland epithelial cells (HMGECs). During serum-induced differentiation for 1 to 6 days, HMGECs drastically enhanced intercellular cohesion, whereas lipid production did not change. The expression profiles of the desmosomal PV antigens desmoglein (Dsg) 3 and 1 but not of the adherens junction component E-cadherin (Ecad) was dependent on the presence of serum. Surprisingly, after 1 day but not after 6 days of serum-induced differentiation, an inhibitory antibody against Ecad drastically reduced intercellular cohesion and blocked lipid production of HMGECs. In contrast, antibodies against desmosomal cadherins, including human and mouse pemphigus autoantibodies, had no effect on monolayer integrity and lipid production. Because lipid production was unaltered in meibomian glands from Dsg3-deficient mice, we established an ex vivo slice culture model of human eyelids to allow studies in a more physiologic environment. Here, the inhibitory antibody against Ecad but not a Dsg3-specific PV antibody interfered with stimulated lipid production. Together, these data demonstrate that cell cohesion is maintained differently in meibomian gland cells and indicate that Ecad is important for meibomian gland function.

Organotypic Culture of Mouse Meibomian Gland: A Novel Model to Study Meibomian Gland Dysfunction In Vitro

“…Recently, another in vitro slice culture model of the human eyelid was established for studying the function of E-cadherin on meibomian glands. 25 However, this method is not suitable for studying ductal system because it may damage the integrity of meibomian gland ducts.…”

Current Advances in Mechanisms and Treatment of Dry Eye Disease: Toward Anti-inflammatory and Immunomodulatory Therapy and Traditional Chinese Medicine

“…The most highly expressed gene in the meibomian gland is the leukocyte-associated immunoglobulin-like receptor, an inhibitory receptor that inhibits immune cell activation and reduces the production of pro-inflammatory cytokines ( 80 ). Moreover, the immunoglobulin-like receptor gene expression is upregulated upon epithelial cell differentiation in the human meibomian gland ( 81 ). Recently, researchers have also found that human meibomian gland epithelial cell lysates inhibit the growth rate of gram-negative bacteria and pseudomonas aeruginosa ( 57 ).…”

Candidate Molecular Compounds as Potential Indicators for Meibomian Gland Dysfunction

“…Cadherins (subtypes of classical cadherins, E-, N-, and P-cadherin) are cell surface glycoproteins involved in calcium-dependent heterotypic and homotypic cell-cell adhesion ( 54 ). In one study, it was demonstrated that N-cadherin occurs in all layers of the cells in the skin epidermis, mucocutaneous junction, and conjunctiva ( 108 ). It is also present in the acini and ductal epithelium of the meibomian glands ( 54 , 108 ).…”