title: 1,25-dihydroxyvitamin D3 inhibits corneal wound healing in an ex-vivo mouse model.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Ophthalmology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Saadettin
authors.initials: S
authors.lastname: Sel
authors.affiliation: Department of Ophthalmology, Martin Luther University Halle-Wittenberg, Halle/Saale, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Trau
authors.affiliation: Department of Anatomy II, University of Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Paulsen
authors.affiliation: Department of Pathology, Otto von Guericke University Magdeburg, Leipziger Str. 44, D-39120, Magdeburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kalinski
authors.affiliation: Institute of Agricultural and Nutritional Sciences, Martin Luther University Halle-Wittenberg, Halle/Saale, Germany.
authors.forename: Gabriele I
authors.initials: GI
authors.lastname: Stangl
authors.affiliation: Department of Ophthalmology, Martin Luther University Halle-Wittenberg, Halle/Saale, Germany. norbert.nass@med.ovgu.de.|Department of Pathology, Otto von Guericke University Magdeburg, Leipziger Str. 44, D-39120, Magdeburg, Germany. norbert.nass@med.ovgu.de.
authors.forename: Norbert
authors.identifier: http://orcid.org/0000-0003-2563-0386
authors.initials: N
authors.lastname: Nass
mesh_terms: D000287:Administration, Topical; D000818:Animals; D002057:Burns, Chemical / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D002117:Calcitriol / Q000008:administration & dosage / Q000494:pharmacology*; D002460:Cell Line; D003316:Corneal Diseases / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D019573:Epithelium, Corneal / Q000187:drug effects / Q000378:metabolism; D005126:Eye Burns / Q000139:chemically induced*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics; D062326:Re-Epithelialization / Q000187:drug effects; D060888:Real-Time Polymerase Chain Reaction; D000067759:Receptor for Advanced Glycation End Products / Q000235:genetics / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism; D047488:Retinoid X Receptors / Q000235:genetics / Q000378:metabolism; D012972:Sodium Hydroxide; D065668:Vitamin D3 24-Hydroxylase / Q000235:genetics / Q000378:metabolism; D014815:Vitamins / Q000008:administration & dosage / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D015850:Interleukin-6; D012333:RNA, Messenger; D000067759:Receptor for Advanced Glycation End Products; D018167:Receptors, Calcitriol; D047488:Retinoid X Receptors; D014815:Vitamins; D012972:Sodium Hydroxide; C585550:Cyp24a1 protein, mouse; D065668:Vitamin D3 24-Hydroxylase; D002117:Calcitriol
keywords: 1,25-dihydroxyvitamin D3; Corneal wound healing; Ex-vivo model; Human corneal epithelial cells; Scratch assay