Viral delivery of heme oxygenase-1 attenuates photoreceptor apoptosis in an experimental model of retinal detachment.

Abstract

This study was designed to evaluate the efficacy of subretinal injection of recombinant adeno-associated virus vector expressing heme oxygenase-1 (rAAV-HO-1) in attenuating photoreceptor apoptosis induced by experimental retinal detachment (RD) in Sprague-Dawley rats. Our results disclosed that subretinal rAAV-HO-1 delivery achieved localized high HO-1 gene expression in retinal outer nuclear layer (ONL) compared with rAAV-lacZ-injected eyes and eyes with RD left untreated both at 2 (p=0.003) and 28 (p=0.007) days of RD. The ONL thickness (p=0.018) and mean photoreceptor nuclei count (p=0.009) in eyes receiving rAAV-HO-1 injection was significantly higher than in rAAV-lacZ-injected or eyes with RD left untreated at 28 days of RD. There were fewer apoptotic photoreceptor nuclei at 2 (p=0.008) and 5 (p=0.018) days of RD and less activated caspase-3 expression (p=0.008) at 2 days of RD in rAAV-HO-1 treated eyes than in control eyes. These data supported that gene transfer approach might attenuate photoreceptor apoptosis caused by RD with a resultant better ONL preservation.