Meibomian Gland Dysfunction: What Have Animal Models Taught Us?

Abstract

Studies have estimated that currently 344 million people worldwide and 16.4 million adults in the US have some form of dry eye disease (DED). It is believed that approximately 70% of DED cases are due to some form of evaporative dry eye, for which Meibomian gland dysfunction (MGD) is the major cause. Unfortunately, currently there is no effective treatment for MGD, and solely palliative care is available. Given the importance of MGD in DED, there has been a growing interest in studying Meibomian gland development, homeostasis and pathology, and, also, in developing therapies for treating and/or preventing MGD. For such, animal models have shown to be a vital tool. Much of what is known today about the Meibomian gland and MGD was learnt from these important animal models. In particular, canine and rabbit models have been essential for studying the physiopathology and progression of DED, and the mouse model, which includes different knockout strains, has enabled the identification of specific pathways potentially involved in MGD. Herein, we provide a bibliographic review on the various animal models that have been used to study Meibomian gland development, Meibomian gland homeostasis and MGD, primarily focusing on publications between 2000 and 2020.

Epithelial stem cell homeostasis in Meibomian gland development, dysfunction, and dry eye disease

“…Meibomian gland dysfunction accounts for the majority of reported dry eye disease cases, and there is an urgent need to develop effective therapies for this condition. Unfortunately, while the morphological development of Meibomian glands is well described, the cell dynamics underlying Meibomian gland dysfunction-mediated dry eye disease remain poorly elucidated (9).…”

“…Several reports have described the generation of animal models to mimic the physiological features observed in human Meibomian gland dysfunction–mediated dry eye disease (reviewed in refs. 9 , 36 ). In some of these models, Meibomian gland function was altered through mechanical interventions or chemical treatments.…”

“…(Figure 2A-D). This indicated that the corneal phenotype we observed in Krox20-cKO mice was due to extrinsic factors, and could possibly be a secondary effect due to Meibomian gland malfunction or defect, since hyperkeratinization of the cornea can result from Meibomian gland dysfunction (9,13). We therefore harvested the eyelids of these mice for analysis of the Meibomian glands.…”

“…Meibum secreted from the Meibomian glands functions to maintain moisture on the ocular surface by protecting the aqueous layer from evaporation, while also protecting the eye from environmental threats and infections ( 7 , 8 ). Hence, when meibum production is compromised by Meibomian gland dysfunction, the tear film is destabilized, resulting in evaporative dry eye disease, the most common type of dry eye disease ( 9 ).…”

“…Meibomian gland dysfunction encompasses a variety of conditions characterized by a defect in Meibomian gland function and accounts for approximately 87% of dry eye disease cases ( 9 , 13 ). The clinical manifestations of Meibomian gland dysfunction include eye irritation and distress and traces of ocular inflammation ( 13 , 14 ).…”