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Mingxia Sun, Sudan Puri, Geraint J Parfitt, Kazadi Nadine Mutoji, Tarsis Ferreira Gesteira, Vivien Jane Coulson-Thomas; Hyaluronan regulates Meibomian gland morphogenesis. Invest. Ophthalmol. Vis. Sci. 2019;60(9):4161.
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© ARVO (1962-2015); The Authors (2016-present)
The Meibomian gland (MG) produces the lipid layer of the tear film, and changes to the MG that lead to a decrease or alteration in lipid quality/content may lead to MG dysfunction, a major cause of evaporative dry eye disease with prevalence ranging from 39% to 50%. Our study aims to investigate the role of hyaluronan (HA), a major extracellular matrix component, in MG development and function.
Hyaluronan synthase (Has) knockout mice were generated: Has1 and Has3 null mice were bred to generate HAS1−/−; HAS3−/− mice and a conditional HAS2 -/ - MG knockout mouse that targeted Has2 deletion in Meibomian gland upon doxycycline induction. Eyelids from adult mice were used for whole mount staining. Tarsal plates were isolated for immunostaing. Tet-off H2B-GFP/K5tTA mice and 5-ethynyl-2′-deoxyurdine (EdU) incorporation were used to determine the role of HA in maintaining slow-cycling cells (SCCs) and proliferating cells within the MG, respectively.
Has knockout mice present hyperplastic dysmorphic MGs, which present primarily cytoplasmic PPARg staining, whereas wt mice present primarily nuclear PPARg staining. The expression of PPARg by qPCR increased 1.6-1.8 fold in the mutant when compared to wt mice. Whole mount analysis revealed that HA forms an intricate 3D HA network surrounding the basal cells of the MG acini, which is up-regulated and presents altered ultrastructure in the mutant mice. Interestingly, proliferating cells, CD44+ cells and H2B-GFP+ SCCs are embedded within this HA matrix.
HA plays an important role in MG development. Our findings suggest that Has knockout mice have abnormal HA synthesis, which in turn leads to precocious and exacerbated MG morphogenesis culminating in dysmorphic eyelids and MGs.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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