Nrf-2 activator sulforaphane protects retinal cells from oxidative stress-induced retinal injury

Abstract

• Retinal ischaemia-reperfusion (IR) injury induces oxidative stress and cell damage. • Sulforaphane activates detoxifying enzymes and suppresses inflammation in cell model. • Sulforaphane preserves retinal function in the rat model of retinal IR injury. • Protective effects originate from upregulation of Nrf2 and downregulation of NF-kB. Retinal ischaemia-reperfusion (IR) injury is implicated in many sight-threatening diseases. The reperfusion of tissue induces oxidative stress and cell damage. Sulforaphane, which is abundant in cruciferous vegetables, exerts anti-oxidative effects. We investigated the protective effect of sulforaphane against oxidative stress or IR injury in retinal cells. We utilized ARPE-19 cells and used tert -butyl hydroperoxide to induce oxidative stress. Cell survival improved after sulforaphane treatment. Sulforaphane attenuated reactive oxygen species production and diminished mitochondrial dysfunction. Furthermore, sulforaphane activated phase II detoxification enzymes and suppressed pro-inflammatory mediators. We transiently raised the intraocular pressure of rats to establish a model of retinal IR injury. High-dose sulforaphane pretreatment ameliorated b-wave decrement in electroretinogram, indicating that sulforaphane could preserve retinal function. Electrophoretic mobility shift assay revealed that these effects originated from upregulation of Nrf2 and downregulation of NF-kB pathway. Our results demonstrated that sulforaphane has a dose-dependent protective effect against oxidative stress and IR injury.