Apoptosis - blocking agents protect the retina from ischemic injury in vivo

Purpose: We have previously demonstrated that transient retinal ischemia results in apoptosis. The purpose of this study was to determine if agents that inhibit apoptosis afford protection in this animal model of transient retinal ischemia. Method: Transient retinal ischemia was produced in Sprague-Dawley rats by raising IOP to greater than systemic pressure for 60 minutes. ERG's were obtained at baseline and at 1 and 7 days after reperfusion. The eyes were enucleated 7 days after reperfusion and examined histopathologically. All drugs were administered intravitreally 24 hours prior to the onset of ischemia. Intravitreal injection of vehicle prior to the induction of ischemia served as controls. Results: Pretreatment with the endonuclease inhibitor aurintricarboxylic acid (ATA) (50 uM) resulted in preservation of the latency and amplitude of the ERG-b wave at 1 and 7 days after reperfusion as compared to ischemic control (we have previously shown histologic preservation in this paradigm). Pretreatment with the RNA synthesis inhibitor Actinomycin D (.2ug/ml) also resulted in preservation of the ERG-b wave. The results of histopathologic analysis will be presented. Conclusions: These data support the hypothesis that transient retinal ischemia may result in apoptotic cell death and agents that inhibit apoptosis may offer new therapeutic strategies to treat this disorder.