Redox survival signalling in retina-derived 661W cells

Reactive oxygen species have been implicated in processes involving cellular damage and subsequent cell death, especially in organs such as the eye that are constantly exposed to excitatory signals. However, recent studies have shown that oxidant species can also act as intracellular signalling molecules promoting cell survival, but little is known about this mechanism in the retina. The present study demonstrates for the first time that hydrogen peroxide (H(2)O(2)) is generated rapidly and acts as a prosurvival signal in response to a variety of apoptotic stimuli in retina-derived 661W cells and in the retinal ganglion cell line RGC-5. Focussing on 661Ws and serum deprivation, we systematically investigated pro-survival and pro-death pathways and discovered that the rapid and transient burst of H(2)O(2) activates the AKT survival pathway. Activation of the apoptotic machinery takes place following the decline of H(2)O(2) to basal levels. To substantiate this proposed pro-survival role of H(2)O(2), we inhibited the oxidant burst, which exacerbated cell death. Conversely, maintenance of the oxidant signal using exogenous H(2)O(2) enhanced cell survival. Overall, the results presented in this study provide evidence for a novel role of H(2)O(2) in mediating survival of retinal cells in response to apoptotic stimuli.