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Publication : Spontaneous acinar and ductal regrowth after meibomian gland atrophy induced by deletion of FGFR2 in a mouse model.

First Author  Yang X Year  2022
Journal  Ocul Surf Volume  26
Pages  300-309 PubMed ID  34798325
Mgi Jnum  J:375681 Mgi Id  MGI:8264791
Doi  10.1016/j.jtos.2021.11.005 Citation  Yang X, et al. (2022) Spontaneous acinar and ductal regrowth after meibomian gland atrophy induced by deletion of FGFR2 in a mouse model. Ocul Surf 26:300-309
abstractText  PURPOSE: We have demonstrated that deletion of fibroblast growth factor receptor 2 gene (Fgfr2) leads to Meibomian gland (MG) atrophy in an inducible conditional knockout mouse model, referred as Fgfr2(CKO). Herein, we investigated whether MG spontaneously recovers after atrophy in this model. METHODS: Two months old Fgfr2(CKO) mice were injected peritoneally once or twice of doxycycline (Dox) at 80 mug/gm of body weight to induce MG atrophy of various severities via Fgfr2 deletion. Recovery of acinar and ductal tissues was monitored by meibography, lipid staining and immunofluorescence against keratin-6a in MG whole-mount. Biomarkers for acinar and ductal differentiation and proliferation were also examined by immunostaining. RESULTS: Single Dox injection in Fgfr2(CKO) mice caused severe acinar and moderate ductal atrophy. Severe ductal shortening or loss occurred after second Dox injection, presumably related to the reported slower cycling of the ductal epithelia. Spontaneous acinar regrowth after atrophy was observed over a period of 60 days in both injection regimens. However, less robust acinar recovery was associated with more disrupted ductal structures in twice injected Fgfr2(CKO) mice. CONCLUSIONS: Our current findings further substantiate the role of FGFR2 in MG homeostasis, and suggest that FGFR2-signaling may provide a potential strategy for regenerating acini from age-related MG dysfunction in humans. Our data demonstrated that spontaneous MG recovery depends on the extent of ductal atrophy, suggesting that ductal epithelia may provide the progenitor cells for acinar regeneration. Nonetheless, the role of ductal tissue as the source of acinar progenitors awaits further investigation.
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