Edaravone protects the retina against ischemia/reperfusion‑induced oxidative injury through the PI3K/Akt/Nrf2 pathway

Xu,Yi‑Pin; Han,Fang; Tan,Jian

doi:10.3892/mmr.2017.7739

Edaravone protects the retina against ischemia/reperfusion‑induced oxidative injury through the PI3K/Akt/Nrf2 pathway

Authors:
- Yi‑Pin Xu
- Fang Han
- Jian Tan
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Affiliations: Department of Plastic Surgery, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, P.R. China
Published online on: October 6, 2017 https://doi.org/10.3892/mmr.2017.7739
Pages: 9210-9216

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Abstract

Retinal ischemia/reperfusion (I/R) injury can occur as a result of a number of ocular diseases or ischemic events in the brain, leading to possible vision loss if not treated properly. The overproduction of reactive oxygen species is important in the process of I/R injury. Edaravone, a free radical scavenger, has been demonstrated to have a neuroprotective effect in cerebral ischemia; however, its effect against retinal I/R injury remains to be fully elucidated. Therefore, the present study investigated the effects of edaravone on the oxidative parameters, retinal inflammation and apoptosis induced by I/R injury, and treated photoreceptor‑derived 661W cells with hydrogen peroxide (H2O2) and edaravone to examine the underlying mechanism. For the in vivo study, oxidative parameters (malondialdehyde, DNA fragmentation, total antioxidant status, superoxide dismutase and glutathione) in the retina, retinal thickness, and apoptotic index in the ganglionic cell layer and inner nuclear layer were measured. For the in vitro study, the effects of edaravone or nuclear factor erythroid‑2‑related factor 2 (Nrf2) small interfering RNA or phosphatidylinositol 3‑kinase (PI3K)/Akt inhibitors on cell viability, membrane integrity, levels of phosphorylated‑Akt, Akt and nuclear Nrf2 of H2O2‑treated 661W cells were examined. The results demonstrated that edaravone inhibited the oxidative injury in the retina induced by the retinal I/R procedure and increased retinal inflammation, and apoptosis. The results of the in vitro experiments demonstrated that edaravone effectively protected the viability and the membrane integrity of the H2O2‑treated 661W cells via the phosphatidylinositol 3‑kinase (PI3K)/Akt/Nrf2pathway. These results indicated the potential protective effect of edaravone against retinal I/R injury and provided a novel explanation for the protective effects of edaravone.

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