RRC ID 38509
著者 Shimazaki H, Hironaka K, Fujisawa T, Tsuruma K, Tozuka Y, Shimazawa M, Takeuchi H, Hara H.
タイトル Edaravone-loaded liposome eyedrops protect against light-induced retinal damage in mice.
ジャーナル Invest Ophthalmol Vis Sci
Abstract PURPOSE: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.
巻・号 52(10)
ページ 7289-97
公開日 2011-9-21
DOI 10.1167/iovs.11-7983
PII iovs.11-7983
PMID 21849425
MeSH Animals Antipyrine / administration & dosage Antipyrine / analogs & derivatives* Cell Line Drug Delivery Systems Edaravone Electroretinography Free Radical Scavengers / administration & dosage* Humans In Situ Nick-End Labeling Light / adverse effects* Liposomes Mice Ophthalmic Solutions / administration & dosage Radiation Injuries, Experimental / etiology Radiation Injuries, Experimental / metabolism Radiation Injuries, Experimental / prevention & control* Reactive Oxygen Species / metabolism Retina / metabolism Retina / radiation effects* Retinal Degeneration / etiology Retinal Degeneration / metabolism Retinal Degeneration / prevention & control*
IF 3.47
引用数 34
WOS 分野 OPHTHALMOLOGY
リソース情報
ヒト・動物細胞 HCE-T(RCB2280)