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

Xiaowei Yang, Xingwu Zhong, Andrew JW Huang, Lixing W. Reneker

Research output: Contribution to journalArticlepeer-review

Abstract

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 Fgfr2CKO. Herein, we investigated whether MG spontaneously recovers after atrophy in this model. Methods: Two months old Fgfr2CKO mice were injected peritoneally once or twice of doxycycline (Dox) at 80 μg/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 Fgfr2CKO 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 Fgfr2CKO 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.

Original languageEnglish
JournalOcular Surface
DOIs
StateAccepted/In press - 2021

Keywords

  • Blepharitis
  • dry eye
  • FGFR2
  • Knockout mouse
  • Meibomian gland
  • Meibomian glands dysfunction
  • Regeneration

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