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Mindy Call, Katy Fischesser, Vivien J Coulson-Thomas, Suohui Zhang, Winston W Y Kao; Regulation of Meibomian Gland Formation and Function. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3199.
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Meibomian gland dysfunction is a chronic abnormality of the meibomian glands characterized by terminal duct obstruction and/or changes in glandular secretion resulting in alterations of the tear film, eye irritation and inflammation. The meibomian glands, which are large sebaceous glands, secrete lipids that comprise the main component of the lipid layer of the tear film. The lipid layer is important for preventing evaporation of the aqueous layer of the tear film and is thought to stabilize the tear film by lowering surface tension. The proper development of this holocrine gland is essential for the production and deposition of lipids onto the surface of the eye. The purpose of this study is to examine the molecular mechanism responsible for the formation and function of the meibomian glands.
To assess the mechanism responsible for proper formation and function of the meibomian glands both in vitro and in vivo models were utilized. An immortalized human meibomian gland cell line was used to examine the role of the Notch and PPARγ pathways in meibomian acinar cell differentiation. For in vivo assessment, transgenic mouse models utilizing both Le-cre and K14-rtTA driver mice, were used to ablate PPARγ, Jag1 and Ext1 as well as to express dnMAML. Animals were examined for signs of MGD/dry eye as well as the expression of Notch, EGF and PPARγ signaling components and proliferation.
Inhibition of the notch signaling pathway using dnMAML and Jag1 mice resulted in significant meibomian gland defects with a phenotype similar to what was seen in the absence of PPARγ including fewer and more condensed lipid droplets, acinar hyperplasia and decreased PPARγ expression. Reduction of lipid and PPARγ was also observed in vitro upon inhibition of Notch signaling. In addition, Ext1 appears to be important for meibomian gland formation as loss of Ext1 resulted in an increase in the number of ductules.
A key component of lipid production is PPARγ and without it meibomian gland dysfunction-like symptoms arise. Notch signaling as well as EGFR signaling appear to be the key components in the regulation of PPARγ and gland formation, respectively. Together these data provide insight into the molecular mechanism behind the formation and function of the meibomian gland.
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