Edaravone-Loaded Liposome Eyedrops Protect against Light-Induced Retinal Damage in Mice
Edaravone-Loaded Liposome Eyedrops Protect against Light-Induced Retinal Damage in Mice
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DOI：
10.1167/iovs.11-7983
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发表时间：
2011-09-01
影响因子：
4.4
通讯作者：
Hara, Hideaki
中科院分区：
文献类型：
--
作者：
Shimazaki, Hiroki;Hironaka, Kohei;Hara, Hideaki
目的。目的研究伊达拉奉(3-甲基-1-苯基-2-吡唑啉-5-1)脂质体滴眼液对小鼠视网膜光损伤的保护作用。方法采用醋酸钙梯度法制备亚微米级脂质体(SsLips)。用8000Lux白光照射暗适应小鼠3小时，造成小鼠视网膜损伤。将载依达拉奉的SSLips分别在光照前后滴入左眼，然后在光照后每天三次，连续5天。通过记录暗适应视网膜电信号(ERG)、测量外核层厚度(ONL)和末端脱氧核苷酸转移酶dUTP缺口末端标记(TUNEL)染色来评价视网膜损伤。用小鼠视锥感光细胞系(661W)测定了载依达拉奉SSLips对活性氧(ROS)的清除能力。结果：与空白对照组相比，Edaravone负载的SSLips滴眼液显著抑制了5d后闪光ERG的a波和b波振幅的降低以及ONL的收缩。载药依达拉奉的SSLips可阻止光照48小时后TUNEL阳性细胞数量的增加。在用游离依达拉奉治疗的组中没有发现这种明显的保护作用。与游离依达拉奉相比，负载依达拉奉的SSLips对体外光诱导的ROS产生和细胞死亡具有更强的抑制作用。SSLips对眼细胞的毒性较小。结论：依达拉奉负载的SSLips滴眼液对光诱导的视网膜功能障碍有保护作用。脂质体滴眼液可能成为眼球后段给药的候选药物之一。(投资眼科VS科学。2011年；52：7289-7297)doi：10.1167/iovs.11-7983
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. (Invest Ophthalmol Vis Sci. 2011;52:7289-7297) DOI:10.1167/iovs.11-7983