Primary cilia regulate Meibomian glands development and dimensions without impairing lipid composition of the meibum

Abstract

PurposePrimary cilia regulate the development of various ectoderm-derived tissues, including the corneal epithelium, skin, hair follicle and sebaceous glands. We aimed to investigate their role in meibomian gland (MG) development.MethodsPrimary cilium ablation in MGs was achieved by crossing a floxed Ift88 mouse (Ift88fl/fl) with a mouse expressing the Cre recombinase under the keratin 14 (K14) promoter, to generate K14-Cre;Ift88fl/fl mice. MG morphology was evaluated by histology and immunostaining, as well as lipid staining and 2-photon microscopy on whole mount tarsal plates. MG lipid profiles were assessed by chromatography.ResultsWe showed that most of MG cells are ciliated during early stages of MG development and that MG ciliated rate decreases throughout morphogenesis. In morphologically mature glands, only the MG central duct and ductules are ciliated, and meibocytes lose their cilia as they differentiate and become filled with lipids. Primary cilium ablation induces enlargement of MGs, dilation of the MG central duct, and an increased production of lipids, without dramatically changing the lipid profiles. In addition, primary cilia regulate MG elongation and the spatial distribution of proliferating and dying cells within MGs, without changing the total cell proliferation and death rates.ConclusionsThese findings indicate that primary cilia are not necessary for normal MG development. However, they promote MG enlargement and lipid production, suggesting that primary cilia could be an interesting target for treatments of ocular surface diseases involving MGs, like dry eye disease.