Abstract
Purpose:
Age-related Macular Degeneration (AMD), which is characterized by choroidal neovascularization (CNV), is the major cause of blindness in advanced countries. Recently, it has been reported that oxidative stress plays a critical role in developing CNV. In Japan, edaravone, a free radical scavenger, is used as a treatment for cerebral infarction. Therefore, the aim of this study was to evaluate the effect of edaravone against laser-induced CNV in mice and to clarify the mechanism.
Methods:
In vivo, 8-week-old-male C57BL/6J mice were used. They were received six laser photocoagulations around the optic disc under anesthesia. They were injected intraperitoneally with 0.3, 1, 3 mg/kg of edaravone just after laser photocoagulation and then twice a day for 2 weeks or intravenously with 3, 10 mg/kg of edaravone in a single dose just after laser photocoagulation. Fundus fluorescein angiography (FFA) was performed 7, 14 days after laser photocoagulation. On day14 after the FFA, 20 mg/mL of fluorescein isothiocyanate-dextran was injected via the tail vein, then the eyes were enucleated and the retinal pigment epithelium (RPE) choroid/sclera flatmounts were prepared. The CNV was measured by confocal microscope and analyzed the CNV area. In vitro, the effect of edaravne against vascular endothelial growth factor (VEGF)-induced cell proliferation was evaluated using human retinal microvascular endothelial cells (HRMECs) and against the H2O2-induced reactive oxygen species (ROS) production was evaluated using ARPE-19 cells.
Results:
In vivo, the area of laser-induced CNV was significantly reduced by itraperitoneal or intravenous injection of edaravone in a dose-dependent manner. In vitro, edaravone significantly inhibited the cell proliferation induced by VEGF in HRMECs and ROS production induced by H2O2 in ARPE-19.
Conclusions:
In the present study, we have shown that edaravone has an inhibitory effect on CNV formation and the mechanism seems to be reduction of cell proliferation and ROS production. These data indicate that edaravone, a free radical scavenger, become one of the potential candidates for the treatment of AMD.
Keywords: 412 age-related macular degeneration •
453 choroid: neovascularization