Function of Vitamin D at the Ocular Surface and Its Role during Corneal Inflammation
Reins, Rose 1976-
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Although first recognized for its role in calcium regulation and bone health, there has been an explosion of research demonstrating that vitamin D is an important modulator of the immune system. In the eye, studies have shown that deficiencies in vitamin D and genetic differences in vitamin D-related genes have a significant impact on the development of various ocular diseases. Vitamin D has been used effectively as a treatment for inflammatory conditions in many tissues, as well as in the eye, attenuating the progression of uveitis, for example. However, up until now, few studies have examined the role of vitamin D at the front part of the eye, the cornea. Maintenance of corneal transparency is essential for vision, and therefore, limiting inflammatory events is beneficial in this tissue. The work contained in this dissertation demonstrates that vitamin D is activated by corneal epithelial cells and is able to regulate gene expression in these cells, including enhancing antimicrobial peptide production. Vitamin D also modulates the inflammatory response to pattern recognition receptor stimulation, by increasing initial cytokine levels and then acting to dampen pro-inflammatory signals later in the response. In vivo, the use of topical vitamin D was explored both during experimental dry eye and in a mouse model of corneal wound healing. Although vitamin D increased tear production in normal mice, a protective effect on the ocular surface, wound healing was delayed and inflammatory signs augmented with vitamin D treatment after epithelial abrasion. These studies fill a gap in knowledge about vitamin D at the ocular surface and highlight the need for research into the immunomodulatory functions of the hormone in the ultimate goal of using vitamin D therapeutically for corneal inflammation.