title: Effects of all-trans retinoic acid nanoparticles on corneal epithelial wound healing.
abstract: BACKGROUND
  We have developed inorganically-coated all-trans retinoic acid (atRA) nanoparticles, nano-sized egg-like particles of atRA (NANOEGG®-atRA). The purpose of this study was to determine the effects of NANOEGG®-atRA on corneal wound healing in vivo and in vitro.
  
  
  METHODS
  A rabbit corneal epithelial wound healing model was exposed to different concentrations of NANOEGG®-atRA. Wound healing was serially quantified as the ratio of fluorescein-stained area at the selected times to that at baseline. After wound closure, the barrier function of the cornea was determined using low concentrations of tropicamide. At the completion of the experiments, the corneal epithelium was histologically examined. For the in vitro studies, linear scratch wounds were made on cultured SV40-immortalized human corneal epithelial cells (HCE-T). Then, the cells were exposed to different concentrations of NANOEGG®-atRA, and wound healing was determined by the degree of closure of the scratch wound. In addition, the effects of NANOEGG®-atRA on the proliferation of HCE-T cells were determined by WST-8 assays.
  
  
  RESULTS
  Exposure to NANOEGG®-atRA decreased the injured area 24 hrs after the ablation. The maximum effect of NANOEGG®-atRA was observed at a concentration of 33 mM. Histologically, no abnormal or differentiated corneal epithelial cells were observed in the histological sections treated with NANOEGG®-atRA. The tropicamide-induced pupillary dilation was significantly slowed in the eyes treated with NANOEGG®-atRA. NANOEGG®-atRA at concentrations of 3.3 and 33 nM induced earlier wound closure in vitro, but did not induce proliferation of HCE-T cells.
  
  
  CONCLUSIONS
  NANOEGG®-atRA promotes wound healing and should be considered for the treatment of wounds of the corneal epithelium.
authors: Department of Ophthalmology, Osaka Medical College, 2-7 Daigaku-machi, 569-8686, Takatsuki, Osaka, Japan.
authors: Masako
authors: M
authors: Hattori
authors: Kazuhiro
authors: K
authors: Shimizu
authors: Kozo
authors: K
authors: Katsumura
authors: Hidehiro
authors: H
authors: Oku
authors: Yoichiro
authors: Y
authors: Sano
authors: Kayo
authors: K
authors: Matsumoto
authors: Yoko
authors: Y
authors: Yamaguchi
authors: Tsunehiko
authors: T
authors: Ikeda
mesh_terms: D000818:Animals; D001692:Biological Transport; D002465:Cell Movement; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003315:Cornea / Q000187:drug effects* / Q000378:metabolism; D065306:Corneal Injuries; D004195:Disease Models, Animal; D004337:Drug Carriers; D019573:Epithelium, Corneal / Q000187:drug effects* / Q000378:metabolism; D015590:Fluorophotometry; D007641:Keratolytic Agents / Q000494:pharmacology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D053758:Nanoparticles; D062793:Occludin; D010750:Phosphoproteins / Q000378:metabolism; D011817:Rabbits; D014212:Tretinoin / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects*; D062826:Zonula Occludens-1 Protein
chemical_list: D004337:Drug Carriers; D007641:Keratolytic Agents; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; D010750:Phosphoproteins; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; D014212:Tretinoin