Abstract
Purpose :
Recent studies suggest that sebaceous glands contain a Krt5+/PPARg+ transitional basal cell population that participates in progenitor cell renewal, and differentiation before moving to the suprabasal compartment (Cell Reports 42, 113121, 2023). The purpose of this study was to test if meibomian glands contain a similar transitional basal cell population that is required for maintenance of acinar meibocytes.
Methods :
Frozen sections from 3 and 18 month-old, female C57Bl/6 mouse eyelids were stained with antibodies to Krt5, PPARg and Ki67 to identify transitional basal cells and their proliferative potential. Basal acinar cells were first detected using QuPath and the nuclear expression of PPARg and Ki67 was quantified. Additionally, 8 week-old Lrig1Cre/ERT2/ PPARgfloxed male and female mice along with their littermates (n=5/group) were fed tamoxifen chow for 10 weeks prior to sacrifice. Eyelids were then collected and fixed tissue processed for meibography, immunocytochemistry and paraffin tissue staining.
Results :
A total of 1244 and 585 Krt5+ acinar nuclei were detected in young and old C57BI/6 mice respectively, of which, respectively, 28% and 18% were positive for Ki67 and 65% and, respectively, 52% were positive for PPARg. Of the PPARg+ nuclei, 23% and 13% from young and old mice respectively showed positive Ki67 staining, suggesting that transitional cells likely undergo cell renewal and that there is a significant loss of proliferating transitional cells with age in individual mice (p<0.05). In transgenic mice, deletion of PPARg in Lrig1-Cre expressing cells resulted in meibomian gland atrophy in 3/5 male mice characterized by loss of PPARg expression, shrinkage of detectible acini and ductal hyperplasia. The finding that 2/5 male and 5/5 female mice showed normal meibomian glands suggests that establishment of adult meibocyte progenitor cells is variable and/or different distinct between sexes.
Conclusions :
Meibomian glands, like the sebaceous glands, contain a transitional basal cell population that is Krt5+/PPARg+, shows proliferative potential, and is required for the suprabasal translocation of progenitor cells to form mature meibocytes. Unlike the sebaceous gland, however, adult meibocyte progenitor cells are not driven by expression of Lrig1 in female mice, and their establishment may be different between male and female mice.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.