bcl-2 gene therapy exacerbates excitotoxicity

The protooncogene bcl-2 can block neuronal death from both naturally occurr ing apoptosis and exogenous insults. bcl-2 is therefore a promising candida te for the prevention of excitotoxic neuronal death. Using an adeno-associa ted viral vector, we delivered the bcl-2 gene to the ganglion cell layer of the rat eye. We hypothesized that infection with bcl-2 would protect gangl ion cells against excitotoxic cell death. However, retinal infection with b cl-2 increased ganglion cell susceptibility to both axonal injury and intra vitreal NMDA. Our study-intended to explore the possibility of bcl-2 transd uction as an in vivo therapeutic approach-revealed deleterious effect of bc l-2 transduction.