title: Amelioration of ultraviolet-induced photokeratitis in mice treated with astaxanthin eye drops.
abstract: OBJECTIVE
  Ultraviolet (UV) acts as low-dose ionizing radiation. Acute UVB exposure causes photokeratitis and induces apoptosis in corneal cells. Astaxanthin (AST) is a carotenoid, present in seafood, that has potential clinical applications due to its high antioxidant activity. In the present study, we examined whether topical administration of AST has preventive and therapeutic effects on UV-photokeratitis in mice.
  
  
  METHODS
  C57BL/6 mice were administered with AST diluted in polyethylene glycol (PEG) in instillation form (15 μl) to the right eye. Left eyes were given vehicle alone as controls. Immediately after the instillation, the mice, under anesthesia, were irradiated with UVB at a dose of 400 mJ/cm². Eyeballs were collected 24 h after irradiation and stained with H&E and TUNEL. In an in vitro study, mouse corneal epithelial (TKE2) cells were cultured with AST before UV exposure to quantify the UV-derived cytotoxicity.
  
  
  RESULTS
  UVB exposure induced cell death and thinning of the corneal epithelium. However, the epithelium was morphologically well preserved after irradiation in AST-treated corneas. Irradiated corneal epithelium was significantly thicker in eyes treated with AST eye drops, compared to those treated with vehicles (p<0.01), in a doses dependent manner. Significantly fewer apoptotic cells were observed in AST-treated eyes than controls after irradiation (p<0.01). AST also reduced oxidative stress in irradiated corneas. The in vitro study showed less cytotoxicity of TKE2 cells in AST-treated cultures after UVB-irradiation (p<0.01). The cytoprotective effect increased with the dose of AST.
  
  
  CONCLUSIONS
  Topical AST administration may be a candidate treatment to limit the damages by UV irradiation with wide clinical applications.
authors.affiliation: Laboratory of Ocular Cell Biology and Visual Science, Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Anton
authors.initials: A
authors.lastname: Lennikov
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Kitaichi
authors.forename: Risa
authors.initials: R
authors.lastname: Fukase
authors.forename: Miyuki
authors.initials: M
authors.lastname: Murata
authors.forename: Kousuke
authors.initials: K
authors.lastname: Noda
authors.forename: Ryo
authors.initials: R
authors.lastname: Ando
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ohguchi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kawakita
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Ohno
authors.forename: Susumu
authors.initials: S
authors.lastname: Ishida
mesh_terms: D060433:Administration, Ophthalmic; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D003315:Cornea / Q000166:cytology / Q000187:drug effects* / Q000528:radiation effects; D019610:Cytoprotection; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000528:radiation effects; D019573:Epithelium, Corneal / Q000166:cytology / Q000187:drug effects* / Q000528:radiation effects; D020287:In Situ Nick-End Labeling; D007634:Keratitis / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009883:Ophthalmic Solutions / Q000008:administration & dosage / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects; D014466:Ultraviolet Rays; D024341:Xanthophylls / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D000975:Antioxidants; D009883:Ophthalmic Solutions; D024341:Xanthophylls; C005948:astaxanthine