Abstract
Purpose: :
To investigate whether edaravone (3-methyl1-phenyl-2-pyrazolin-5-one), a free radical scavenger is neuroprotective against photereceptor death in a rat model of retinal detachment (RD).
Methods: :
RD was induced in adult Brown Norway rats by subretinal injection of sodium hyaluronate. Edaravone (3 mg/kg, 5 mg/kg, 10 mg/kg) or physiologic saline were administered intraperitoneally once a day until sacrifice on day 3 or 5. Oxidative stress in the retina was assessed by 4-hydroxynonenal staining or ELISA for protein carbonyl content. Photoreceptor death was assessed by TUNEL and measurement of the outer nuclear layer thickness . Western blot analysis and caspase activity assays were performed. Inflammatory cytokine secretion and inflammatory cell infiltration were evaluated by ELISA and immunostaining, respectively.
Results: :
RD resulted in increased generation of ROS. Treatment with 5 mg/kg edaravone significantly reduced ROS level along with decrease in TUNEL positive cells in the photoreceptor layer. Caspase assay also confirmed decreased activation of caspases -3,-,8, and -9 in RD treated with edaravone. The level of the anti-apoptotic Bcl-2 was increased in detached retinas after edaravone treatment, whereas the levels of the stress-activated p-ERK1/2 were decreased. Additionally, edaravone treatment resulted in a significant decrease in the levels of TNF-α, MCP-1 and macrophage infiltration.
Conclusions: :
Oxidative stress plays an important role in the photoreceptor apoptosis after RD. Edaravone treatment may aid in preventing photoreceptor apoptosis following RD by suppressing ROS-induced photoreceptor damage.
Keywords: retinal detachment • oxidation/oxidative or free radical damage • photoreceptors