1,25-dihydroxyvitamin D3 inhibits corneal wound healing in an ex-vivo mouse model

Graefes Arch Clin Exp Ophthalmol. 2016 Apr;254(4):717-24. doi: 10.1007/s00417-016-3267-4. Epub 2016 Jan 21.

Abstract

Purpose: Impaired healing of corneal injuries can result in ulceration and complete loss of vision, especially in the elderly. Such patients frequently also exhibit vitamin D insufficiency. 1,25-dihydroxyvitamin D3 is the active vitamin D metabolite. As it affects cell proliferation and inflammation, we herein aimed at elucidating its influence on corneal wound healing after alkali burn by using in vitro and ex vivo techniques.

Methods: mRNA abundance in human corneal epithelial cells in response to vitamin D3 was determined by RT-PCR. Corneal re-epithelialization after alkaline burn was analyzed using enucleated mouse eyes and fluorescein staining.

Results: Human corneal epithelial cells (HCEC) expressed the vitamin D receptor (VDR) and retinoid x receptor (RXR) and were responsive to 1,25- dihydroxyvitamin D3, as shown by induction of the 1,25- dihydroxyvitamin D3 responsive gene cyp-24A1 and slightly reduced abundance of IL-6 mRNA. However, no effect on cell vitality and migration was observed. In contrast, re-epithelialization of mouse corneas ex vivo was dose dependently inhibited by 1,25- dihydroxyvitamin D3.

Conclusions: These data indicate that topically applied 1,25- dihydroxyvitamin D3 does not seem to be suitable for therapy of corneal lesions.

Keywords: 1,25-dihydroxyvitamin D3; Corneal wound healing; Ex-vivo model; Human corneal epithelial cells; Scratch assay.

MeSH terms

  • Administration, Topical
  • Animals
  • Burns, Chemical / drug therapy*
  • Burns, Chemical / genetics
  • Burns, Chemical / metabolism
  • Calcitriol / administration & dosage
  • Calcitriol / pharmacology*
  • Cell Line
  • Corneal Diseases / drug therapy*
  • Corneal Diseases / genetics
  • Corneal Diseases / metabolism
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Epithelium, Corneal / drug effects
  • Epithelium, Corneal / metabolism
  • Eye Burns / chemically induced*
  • Humans
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • RNA, Messenger / genetics
  • Re-Epithelialization / drug effects
  • Real-Time Polymerase Chain Reaction
  • Receptor for Advanced Glycation End Products / genetics
  • Receptor for Advanced Glycation End Products / metabolism
  • Receptors, Calcitriol / genetics
  • Receptors, Calcitriol / metabolism
  • Retinoid X Receptors / genetics
  • Retinoid X Receptors / metabolism
  • Sodium Hydroxide
  • Vitamin D3 24-Hydroxylase / genetics
  • Vitamin D3 24-Hydroxylase / metabolism
  • Vitamins / administration & dosage
  • Vitamins / pharmacology*
  • Wound Healing / drug effects*

Substances

  • Interleukin-6
  • RNA, Messenger
  • Receptor for Advanced Glycation End Products
  • Receptors, Calcitriol
  • Retinoid X Receptors
  • Vitamins
  • Sodium Hydroxide
  • Cyp24a1 protein, mouse
  • Vitamin D3 24-Hydroxylase
  • Calcitriol