Abstract
Purpose: :
Goblet cells of the mouse conjunctiva secrete the mucin Muc5AC and to a lesser extent Muc5B. The purpose of this study was to determine if mice null for either of these mucins have an altered ocular surface phenotype.
Methods: :
The ocular surface of mice null for Muc5AC or Muc5B and their wild type (wt) controls were compared grossly and by fluorescein staining. Immunofluorescence microscopy using antibodies to Muc5AC and Muc5B was used to determine if Muc5AC and Muc5B colocalize in the same goblet cell and if there is a compensatory increase of Muc5B in Muc5AC -/- mice and vice versa. Numbers of goblet cells in sections of conjunctiva of -/- and wt mice were assessed by light microscopy. To determine if lack of the Muc5AC mucin enhances desiccating stress on the ocular surface, -/- mice were placed in a controlled environment chamber for 15 days and tear volume and fluorescein staining measured every 3 days.
Results: :
Neither Muc5AC nor Muc5B -/- mice had grossly visible ocular surface abnormalities as compared to wt, however both mucin null mice had significantly increased fluorescein staining compared to wt. In wt conjunctivae, the large majority of goblet cells bound Muc5AC antibodies with only a few goblet cells positive for Muc5B. The mucin antibodies did not colocalize to the same goblet cells suggesting the mucins are made by different cells. There was no substantive increase in immunoreactivity of either Muc5B in the 5AC -/- mice, or 5AC in 5B-/-mice. Surprisingly, numbers of goblet cells per unit area of conjunctival epithelium did not vary between either mucin -/- mouse or their wt suggesting that mucin content alone does not define goblet cell morphology. Exposure of Muc5AC -/- mice to desiccating stress resulted in a significant decrease in tear volume at days 12 and 15 compared to wt. Throughout the 15 day exposure to desiccating stress in the controlled environment chamber, Muc5AC -/- mice had consistently higher fluorescein staining scores compared to wt.
Conclusions: :
Both Muc5AC and Muc5B secreted by mouse conjunctival goblet cells contribute to ocular surface homeostasis.
Keywords: cornea: surface mucins • conjunctiva • cornea: tears/tear film/dry eye