July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Effects of a Topical Vitamin D Analog on Experimental Dry Eye
Author Affiliations & Notes
  • Rose Y Reins
    College of Optometry, Univ of Houston, Houston, Texas, United States
  • Alison M McDermott
    Department of Applied Sciences, Northumbria University, Newcastle upon Tyne, United Kingdom
  • Rachel L Redfern
    College of Optometry, Univ of Houston, Houston, Texas, United States
  • Footnotes
    Commercial Relationships   Rose Reins, None; Alison McDermott, None; Rachel Redfern, None
  • Footnotes
    Support  NIH Grant EY023628 (Redfern)
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 3312. doi:
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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)

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Abstract

Purpose : 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.

Methods : 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.

Results : 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.

Conclusions : 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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