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Rose Y Reins, Alison M McDermott, Rachel L Redfern; Effects of a Topical Vitamin D Analog on Experimental Dry Eye. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3312.
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© ARVO (1962-2015); The Authors (2016-present)
Vitamin D is a natural, multifunctional hormone known to regulate inflammation. Dry eye disease is a leading cause for chronic ocular surface discomfort, damage, and inflammation. Therefore, this study examined (1) the response of corneal cells to the vitamin D analog, calcipotriol; and (2) the effect of topically applied calcipotriol during experimental dry eye (EDE), to evaluate its potential therapeutic role in modulating dry eye inflammation.
Human corneal epithelial cells (hTCEpi) were treated with calcipotriol (10-7M) with TLR agonists or hyperosmolar stress (HOS; 400-500 mOsM/kg) for 24h and RNA and supernatants collected for qPCR and ELISA. Cell viability was evaluated by MTT assay. For EDE, C57BL/6 mice were subjected to desiccating stress (~20% humidity, continuous airflow, and scopolamine hydrobromide injections 3x/d) for 5d. Mice received topical calcipotriol (10-7M, 5µl) or vehicle (0.001% ethanol) twice daily. After 5d, mice were evaluated for phenol red thread test, ocular surface fluorescein staining by OCT, and corneas collected for qPCR and whole eyes for immunohistochemistry.
Following 24h, calcipotriol increased hTCEpi expression of the antimicrobial peptide, LL-37 (4.6x), and vitamin D enzyme, CYP24A1 (3x105x), without affecting cell viability. When treated in combination with TLR agonist Poly(I:C), calcipotriol downregulated IL-6, IL-8, IL-1β, and TNFα expression (15-78%), but did not decrease HOS-induced cytokine levels. In vivo, EDE augmented corneal vitamin D receptor (VDR) and CYP24A1 expression (p<0.01). However, calcipotriol treatment did not affect either fluorescein staining or tear volume. Topical calcipotriol increased expression of the antimicrobial peptide, CRAMP (2.1±0.4x), CXCL1 (3.6±0.9x), and CXCL2 (4.6±1.1x) in the cornea during EDE, but did not have a significant effect on pro-inflammatory cytokine levels.
This study provides insight into the therapeutic role for vitamin D at the ocular surface. Calcipotriol increased antimicrobial peptide expression both in vitro and in vivo, with important implications for protection against infection. Although dampening pro-inflammatory mediators in hTCEpi, calcipotriol did not decrease cytokines during EDE, nor did it reverse ocular surface staining or diminished tear volume. However, EDE did increase vitamin D-responsive genes, suggesting that dry eye increases the ability of the cornea to respond to vitamin D treatment.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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