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HB Paz, A Tisdale, Y Danjo, IK Gipson; Mucin Packaging in the Conjunctival Goblet Cells of Vitamin D Receptor Ablated Mice . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3155.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Recent reports hypothesize that calcium plays an important role in providing cationic shielding to keep negatively charged mucins condensed and tightly packed within mucus granules. Vitamin D controls mineral ion homeostasis and intestinal calcium absorption mediated by the nuclear vitamin D receptor (VDR). Hypocalcemia is observed in mice in which the VDR has been ablated. The ocular surface of VDR ablated mice shows alterations, including mucus strands and ocular surface inflammation. The purpose of this study was to test the hypothesis that calcium is required for the physiological packaging of mucins by comparing the morphology of conjunctival goblet cells in VDR ablated mice to wild type control mice. Methods: Conjunctival tissues from C57/129/sv hybrids VDR ablated mice were obtained from Dr. Marie B. Demay, Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA (Proc. Natl. Acad. Sci. USA 94:9831-9835, 1997). VDR ablated mice fed a diet high in calcium to normalize serum ionized calcium levels were also provided and included as controls. Eyes were fixed in situ, enucleated, fixed for a second time, processed and embedded in methylmethacrylate for light microscopy and in Epon-Araldite for transmission electron microscopy (TEM). To assay conjunctival goblet cell morphology and mucin packets, sections were stained with hematoxylin and eosin, or PAS. Results: Both hematoxylin and eosin, and PAS staining showed an altered pattern of mucin packaging in the goblet cells of VDR ablated mice compared to control mice. In the VDR ablated mice, the mucin packets varied in size and staining density; whereas, in the controls, the secretory granules were highly regular and uniform in size. TEM confirmed the alteration of mucin packets within the conjunctival goblet cells. Packets in the VDR ablated mice showed dispersed fibrillar and less electron dense material compared to the homogeneous and more electron-dense packets in wild type. By TEM the appearance of mucin packets in the VDR ablated mice that had restored calcium levels were comparable to those of the wild type control mice. Conclusion: VDR ablated mice presented altered conjunctival mucin packaging. Restoration of ionized calcium levels in the VDR ablated mice prevented altered mucin packaging, supporting the hypothesis that calcium is required for the physiological packaging of mucins in goblet cells.
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