Dyslipidemia and Meibomian Gland Dysfunction: Utility of Lipidomics and Experimental Prospects with a Diet-Induced Obesity Mouse Model

Abstract

Meibomian gland dysfunction (MGD) is the leading cause of dry eye disease and loss of ocular surface homeostasis. Increasingly, several observational clinical studies suggest that dyslipidemia (elevated blood cholesterol, triglyceride or lipoprotein levels) can initiate the development of MGD. However, conclusive evidence is lacking, and an experimental approach using a suitable model is necessary to interrogate the relationship between dyslipidemia and MGD. This systematic review discusses current knowledge on the associations between dyslipidemia and MGD. We briefly introduce a diet-induced obesity model where mice develop dyslipidemia, which can serve as a potential tool for investigating the effects of dyslipidemia on the meibomian gland. Finally, the utility of lipidomics to examine the link between dyslipidemia and MGD is considered.

Meibomian Gland Dysfunction: What Have Animal Models Taught Us?

“…In recent years, several clinical studies have demonstrated that moderate-to-severe MGD was associated with high total cholesterol and low-density lipoprotein blood levels [85,86]. Thereafter, dyslipidemic animal models were used to study the Meibomian gland and, more specifically, MGD [87][88][89]. To investigate whether systemic lipid disorders can be associated with DED and/or MGD, a study used three transgenic adult mice models, apolipoprotein-E knockout (APOE-KO), low-density lipoprotein receptor knockout (LDLR-KO) and a mouse model with overexpression of human apolipoprotein CIII (ApoCIIIKI), compared to age-and gender-matched C57BL/6 mice [87].…”

Obese Mice with Dyslipidemia Exhibit Meibomian Gland Hypertrophy and Alterations in Meibum Composition and Aqueous Tear Production

“…In the eye, dyslipidemia is also thought to initiate meibomian gland dysfunction (MGD), the leading cause of dry eye disease [ 11 , 12 ]. The meibomian glands are modified sebaceous glands in the eyelids which produce meibum, the tear film lipid component [ 13 ].…”

“…Disruption of the normal lipid composition could also be pro-inflammatory, serving as a potential precursor for blepharitis, which can affect the normal secretory function of the meibomian gland [ 13 , 23 , 24 ]. This can lead to reduced tear film quality and stability and, ultimately, ocular surface inflammation as occurs in MGD and dry eye [ 4 , 11 , 12 , 13 , 16 , 17 , 18 ].…”

“…Over the last decade, the idea has gained momentum that blood plasma lipids affect the meibomian gland [ 12 , 13 , 14 , 17 ]; however, direct experimental evidence for this relationship is lacking. Moreover, one experimental study dating back to 1975 was unable to confirm this relationship [ 25 ].…”

“…Moreover, one experimental study dating back to 1975 was unable to confirm this relationship [ 25 ]. Hence, there is a need to re-examine this relationship using an appropriate experimental approach that includes a suitable animal model and sensitive analytical techniques [ 12 , 13 ].…”