Characterization of Vitamin D at the Ocular Surface and its Association with Dry Eye Disease



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Purpose: Dry eye disease (DED) results in significant ocular surface inflammation and is a leading cause for individuals seeking eye care. Vitamin D has potent anti-inflammatory functions and low serum levels are associated with DED. Very little is known regarding the bioavailability of vitamin D, its receptor (VDR) and regulating enzymes that modulate its activity at the ocular surface. This study evaluated vitamin D levels and its related gene expression under normal and DED conditions. Methods: First, to assess the presence and levels of vitamin D in the human tear film, basal tears were pooled from normal subjects (n=30) and analyzed by mass spectrometry. Next, normal (n=9) and DED (n=11) subjects were recruited to compare vitamin D levels in the tear film (microcapillary tube collection) and conjunctival epithelial cells (impression cytology). VDR, CYP27B1, and CYP24A1 mRNA expression were determined in cell lysates by qPCR. Since hyperosmolar stress (HOS) is a key factor in DED, gene expression was also evaluated in vitro by culturing primary human conjunctival epithelial cells (HConjECs) under HOS (n=3). Basal tear and serum vitamin D levels were measured by mass spectrometry and blood spot analysis, respectively. Results: The active form of vitamin D (1,25D3) was identified in normal human tear samples (3.5 pmol/L). VDR and CYP27B1 mRNA expression were decreased in DED (0.73 ± 0.09 vs 1.1 ± 0.16; P≤ 0.01 and 0.43 ± 0.05 vs 1.06 ± 0.12; P≤ 0.0001, respectively) while CYP24A1 expression did not differ among groups (P=0.65). A significant correlation between CYP27B1 and VDR mRNA expression was found (r= 0.6300, P≤ 0.0001). In primary HConjEC, HOS did not significantly modulate vitamin D related mRNA expression. There was no difference in serum vitamin D between groups. However, tears showed a three-fold increase of active vitamin D metabolites (1,25D3) in DED. Conclusion: Our data suggests that in DED active vitamin D accumulates in tears, however its utilization may be limited by reduced expression of VDR and CYP27B1 activating enzyme. Further studies to understand the modulation of vitamin D bioavailability at the ocular surface and its therapeutic potential in DED are needed.



dry eye, vitamin d, tears, VDR, CYP27B1, CYP24A1