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D.G. Ryan, J.A. Kessler, R.M. Lavker; Loss of BMP Signaling Results in Meibomian Gland Dysplasia and an Altered Palpebral Conjunctival Epithelium . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3157.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Interference in BMP signaling causes generalized abnormalities in cell proliferation, differentiation, and apoptosis. BMP plays a crucial role in the development of appendages (e.g., hair follicles, sebaceous glands). To analyze the in vivo effects of BMP signaling on meibomian gland development, we characterized transgenic mice that ectopically express Noggin, a potent BMP inhibitor. Methods: We generated transgenic mice carrying the murine Noggin cDNA under the control of a neuron specific enolase (NSE) promoter. Mice carrying this transgene express Noggin in melanocytes, which inhibits BMP in nearby cells. Upper and lower eyelids were dissected from transgenic and wild–type mice at various stages of development. Whole mount specimens containing meibomian glands, mucocutaneous junctional (MCJ) epithelium and palpebral conjunctiva as well as frozen and paraffin embedded tissues were examined histologically. The presence of phosphorylated Smads (1, 5, 8), a direct result of BMP signaling was determined immunohistochemically. Results:Phosphorylated Smads, which are normally expressed in the nuclei of meibomian gland acini, ductal epithelia, and MCJ epithelium of wild type mice, were absent from tissues of transgenic mice. Individual meibomian glands were missing or markedly disorganized in the whole mounts prepared from Noggin transgenic mice. This phenotype was more severe in the lower lids and was more pronounced in younger (21 day) animals. Interestingly, we observed a marked increase in the number of goblet cells in the palpebral conjunctival epithelium of Noggin transgenic mice compared with wild type controls that was not age related. Furthermore, the clusters of goblet cells were larger in the palpebral epithelium of the transgenic mice. Conclusions: Loss of BMP signaling affects the normal development of the meibomian gland and conjunctival epithelium. We suggest that BMP signaling is inhibited in the meibomian gland and MCJ epithelium as a result of misexpression of Noggin by melanocytes which are preferentially distributed in the stroma surrounding these tissues. Furthermore, we speculate that it is the inhibition of BMP activity in the MCJ epithelium that contributes to the change in cell fate choice from an epithelial support cell to a goblet cell in the palpebral conjunctival epithelium. This is consistent with the idea that the MCJ epithelium, in part, helps maintain the palpebral conjunctival epithelium.
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