No abstract

Meibomian glands (MGs) are modified sebaceous glands producing the tear film’s lipids. Despite their critical role in maintaining clear vision, the mechanisms underlying MG morphogenesis in development and disease remain obscure. Cilia-mediate signals are critical for the development of skin adnexa, including sebaceous glands. Thus, we investigated the role of cilia in MG morphogenesis during development. Most cells were ciliated during early MG development, followed by cilia disassembly during differentiation. In mature glands, ciliated cells were primarily restricted to the basal layer of the proximal gland central duct. Cilia ablation in keratine14-expressing tissue disrupted the accumulation of proliferative cells at the distal tip but did not affect the overall rate of proliferation or apoptosis. Moreover, impaired cellular patterning during elongation resulted in hypertrophy of mature MGs with increased meibum volume without altering its lipid composition. Thus, cilia signaling networks provide a new platform to design therapeutic treatments for MG dysfunction.

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.