Purchase this article with an account.
Lixing W Reneker, Xiaowei Yang, Xingwu Zhong, Andrew J W Huang; Meibomian Gland (MG) Acinar Regeneration from Atrophy in a Fgfr2 Conditional Knockout Mouse Model. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1412. doi: https://doi.org/.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
We have reported that fibroblast growth factor receptor 2 (Fgfr2) is essential for MG acinar tissue homeostasis and renewal in adult mice (IOVS 2017, 58:2638). In this study, we investigated MG regeneration after severe acinar atrophy triggered by Fgfr2 depletion.
A triple transgenic mouse line (Krt14-rtTA; tetO-Cre, and Fgfr2flox/flox), referred as Fgfr2CKO, was generated, in which Fgfr2 gene can be deleted in keratin 14-expressing cells upon doxycycline (Dox) induction. Two-month old Fgfr2CKO mice were injected intra-peritoneally with Dox at a dosage of 80 µg/gm body weight, either once or twice (one week after the first injection; n>6 in each group). MG morphology were evaluated by a stereomicroscope, and architectures by staining for oil-red-O (ORO) and cytokeratins.
Two weeks after the first Dox injection, severe MG acinar atrophy with reduced meibum production was observed in both groups of Fgfr2CKO mice. MG acinar regeneration was examined at 4 and 8 weeks after initial Dox injection. Recovery to more than 80% of acinar area was noted in Fgfr2CKO mice with only one Dox injection at 8 weeks, when compared with the total acinar area in control (Cre-negative) mice. However, only 30-50% of acinar area in Fgfr2CKO mice twice injected with Dox could be identified, exhibiting a slower MG recovery with delayed glandular regeneration. Histological analyses revealed that the acinar regeneration were affected the integrity of the ductal structure. The internal mesh-like cytostructures of main MG duct were missing in areas with poor acinar regeneration, even though the main duct could still be identified in those areas.
Despite of severe MG atrophy induced by Dox in Fgfr2CKO, MG acini are capable of regeneration upon cessation of Dox. The acinar regeneration seems to depend on the integrity of adjacent MG ductal structures.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
This PDF is available to Subscribers Only