Fibroblast Growth Factor Receptor 2 (FGFR2) Is Required for Meibomian Gland Homeostasis in the Adult Mouse

Investigative Ophthalmology & Visual Science
Lixing W RenekerAndrew J W Huang

Abstract

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. 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. FGFR2 was highly expressed in normal human MGs and adult mouse MGs. Two-month-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 differ...Continue Reading

Citations

Oct 6, 2019·The British Journal of Ophthalmology·Lixing W RenekerAndrew J W Huang
Nov 19, 2019·Ocular Immunology and Inflammation·Deniz MarangozAfsun Sahin
Nov 26, 2020·International Journal of Molecular Sciences·Mingxia SunVivien J Coulson-Thomas
Jul 22, 2019·Experimental Eye Research·Céline PortalJean-Luc Desseyn

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Methods Mentioned

BETA
gene knockout
PCR
Conditional
transgenic

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