PURPOSE. Ischemic stroke in retinal arteries leads to death of neural tissue and ultimately to blindness. The retina is known to die within 4 hours after onset of ischemia. It is debated whether hypothermia might increase the time window for medical treatment and thereby the chance of recovering sight. In order to characterize the time course of cell death during ischemia and potential beneficial effects of hypothermia in more detail, we investigated the survival of ganglion cells in ischemic pig and human retina as a function of time and temperature.METHODS. Eyes were obtained from minipigs and from human donors post mortem. Enucleated minipig eyes were stored for defined durations at three different temperatures (37 degrees C, 21 degrees C, and 4 degrees C). In order to assess the viability of the tissue, we measured ganglion cell activity (spiking) with multielectrode arrays.RESULTS. Minipig retinal ganglion cell function was severely compromised after 2 hours of ischemia at body temperature. After 4 hours, ganglion cells did not fire action potentials anymore. However, at 21 degrees C, ganglion cell activity was maintained under ischemic conditions for up to 12 hours, and for at least 50 hours at 4 degrees C. In postmortem human retina, we recorded ganglion cell activity in retinas received up to 27 hours after death.CONCLUSIONS. Our results demonstrate that hypothermia greatly increases survival of retinal ganglion cells exposed to ischemia. These results might be relevant for the future treatment of retinal ischemia.
