title: Edaravone-loaded liposome eyedrops protect against light-induced retinal damage in mice.
abstract: OBJECTIVE
  To investigate the pharmacologic effects of eyedrops containing liposomes loaded with edaravone (3-methyl-1-phenyl-2-pyrazolin-5-1) against light-induced retinal damage in mice.
  
  
  METHODS
  Edaravone was incorporated into submicron-sized liposomes (ssLips) by the calcium acetate gradient method. Retinal damage in mice was induced in dark-adapted mice by exposure to white light at 8000 lux for 3 hours. Edaravone-loaded ssLips were dropped into the left eye just before and after light exposure and then three times daily for 5 days after light exposure. Retinal damage was evaluated by recording the scotopic electroretinogram (ERG) and measuring the thickness of the outer nuclear layer (ONL) and by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining. The scavenging capacity of reactive oxygen species (ROS) of edaravone-loaded ssLips was determined using a murine cone photoreceptor cell line (661W). The human corneal and conjunctival cell lines were exposed to edaravone-loaded ssLips to determine cytotoxicity.
  
  
  RESULTS
  Eyedrop administration of edaravone-loaded ssLips significantly prevented both the decrease in a- and b-wave amplitudes of flash ERG and the shrinkage of the ONL compared with the control group (treated with empty ssLips) after 5 days of light exposure. The edaravone-loaded ssLips prevented the increase in the numbers of TUNEL-positive cells after 48 hours of light exposure. This marked protection was not found in the group treated with free edaravone. Edaravone-loaded ssLips showed a stronger inhibition of in vitro light-induced ROS production and cell death than did free edaravone. The ssLips showed little cytotoxicity toward ocular cell lines.
  
  
  CONCLUSIONS
  Edaravone-loaded ssLips protected against light-induced retinal dysfunction by eyedrop administration. Liposomal eyedrops may become one of the therapeutic candidates for drug delivery to posterior eye segments.
authors.affiliation: Department of Biofunctional Evaluation, Molecular Pharmacology, Gifu Pharmaceutical University, Gifu, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Shimazaki
authors.forename: Kohei
authors.initials: K
authors.lastname: Hironaka
authors.forename: Takuya
authors.initials: T
authors.lastname: Fujisawa
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tsuruma
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Tozuka
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Shimazawa
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Takeuchi
authors.forename: Hideaki
authors.initials: H
authors.lastname: Hara
mesh_terms: D000818:Animals; D000983:Antipyrine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D002460:Cell Line; D016503:Drug Delivery Systems; D000077553:Edaravone; D004596:Electroretinography; D016166:Free Radical Scavengers / Q000008:administration & dosage*; D006801:Humans; D020287:In Situ Nick-End Labeling; D008027:Light / Q000009:adverse effects*; D008081:Liposomes; D051379:Mice; D009883:Ophthalmic Solutions / Q000008:administration & dosage; D011833:Radiation Injuries, Experimental / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012160:Retina / Q000378:metabolism / Q000528:radiation effects*; D012162:Retinal Degeneration / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*
chemical_list: D016166:Free Radical Scavengers; D008081:Liposomes; D009883:Ophthalmic Solutions; D017382:Reactive Oxygen Species; D000077553:Edaravone; D000983:Antipyrine