Fibroblast growth factor receptor 2 (FGFR2) is required for meibomian gland homeostasis in the adult mouse

Lixing W. Reneker, Lanlan Wang, Rebecca T. Irlmeier, Andrew J.W. Huang

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

PURPOSE. Little is known about the signaling mechanisms controlling meibomian gland (MG) homeostasis and the pathogenic processes leading to MG atrophy and dysfunction in dry eye disease (DED). We investigated the role of fibroblast growth factor receptor 2 (FGFR2) in the MG homeostasis of adult mice. METHODS. A triple transgenic mouse strain (Krt14-rtTA; tetO-Cre; Fgfr2flox/flox), referred to as Fgfr2CKO mice, was generated in which the Fgfr2 gene is ablated by Cre recombinase in keratin 14 (Krt14)-expressing epithelial cells on doxycycline (Dox) induction. FGFR2 expression in normal human and mouse MGs was evaluated by immunohistochemistry. Pathologic MG changes in transgenic mice with conditional deletion of FGFR2 were examined by lipid staining, histology, and immunostaining. RESULTS. FGFR2 was highly expressed in normal human MGs and adult mouse MGs. Twomonth-old Fgfr2CKO mice fed Dox-containing chow for 2 weeks developed severe MG atrophy. MG acinar atrophy in the Fgfr2CKO mice was associated with reduced lipid (meibum) production and the development of clinical findings similar to those in humans with evaporative DED related to MG dysfunction (MGD). Immunohistochemical analyses showed that FGFR2 deletion severely affected proliferation and differentiation of MG acinar cells but affected MG ductal cells to a lesser extent. CONCLUSIONS. FGFR2 deletion results in significant MG acinar atrophy and clinical manifestations of MGD in Fgfr2CKO mice, suggesting that MG homeostasis is FGFR2 dependent. The Fgfr2CKO mice with inducible MG atrophy can serve as a valuable animal model for investigating the pathogenesis of MGD and developing novel therapeutic strategies for MGD-related DED.

Original languageEnglish
Pages (from-to)2638-2646
Number of pages9
JournalInvestigative Ophthalmology and Visual Science
Volume58
Issue number5
DOIs
StatePublished - May 2017

Keywords

  • Dry eye disease
  • FGFR2
  • Knockout animals
  • Meibomian gland atrophy
  • Meibomian gland dysfunction

Fingerprint

Dive into the research topics of 'Fibroblast growth factor receptor 2 (FGFR2) is required for meibomian gland homeostasis in the adult mouse'. Together they form a unique fingerprint.

Cite this