Abstract
Purpose: :
The Meibomian glands are important tissues within the eyelid, which produce and secrete meibum that prevents evaporation of the tear film. The peroxisome proliferator activated receptor gamma (PPARγ) is a member of the nuclear hormone receptor family and is known to play a role in lipid and lipidprotein metabolism. Evidence suggests that PPARγ is important in the production of meibum and changes in the regulation of this molecule have been implicated in Meibomian gland dysfunction. Our study aims to characterize the tissue types contributing to and responsible for the proper development of the Meibomian gland as well as to assess the role of PPARγ for the proper formation of these glands.
Methods: :
Eyelids were removed from C57BL6 mice at various time points ranging from P2 (postnatal day2)-P11. A panel of cytokeratin antibodies was used to identify the various epithelial phenotypes present in the Meibomian gland and at the lid margin in frozen sections. To assess the role of PPARγ, triple transgenic Krt14-rtTA/tet-O-Cre/ PPARγf/f mice were utilized to ablate PPARγ upon doxycycline inductionin epidermal epithelial cells. Eyes were subsequently examined for changes in Meibomian gland morphogenesis and function. All reported research was conducted in compliance with the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research and approved by the IACUC of the University of Cincinnati.
Results: :
The conjunctival marker K4/K13 was found in the conjunctiva as well as in epithelial cells lining the central duct. K10 was present within the superficial layers of the skin epidermis lining the invaginating cord. At P7 a small subset of K10 positive cells were also present in the basal layer of the epidermis. While the ablation of PPARγ in Meibomian glands was incomplete, disorganization of the Meibomian gland was observed including a thickening of the supporting cells and malformed acini. Oil Red O staining did not reveal abnormalities in lipid production in mice three weeks of age.
Conclusions: :
During Meibomian gland development there is perhaps a contribution from a distinct cell lineage expressing both K4/K13 and K1/K10 cytokeratins characteristic of conjuctival and epidermal epithelium. Partial loss of PPARγ results in disorganization of the Meibomian gland and while lipid secretion appears normal it will be interesting to assess these mice as they age to see if loss of PPARγ could contribute to age related meibomian gland dysfunction.
Keywords: cornea: tears/tear film/dry eye • anterior segment • transgenics/knock-outs