title: bcl-2 gene therapy exacerbates excitotoxicity.
abstract: The protooncogene bcl-2 can block neuronal death from both naturally occurring apoptosis and exogenous insults. bcl-2 is therefore a promising candidate for the prevention of excitotoxic neuronal death. Using an adeno-associated 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 ganglion cells against excitotoxic cell death. However, retinal infection with bcl-2 increased ganglion cell susceptibility to both axonal injury and intravitreal NMDA. Our study--intended to explore the possibility of bcl-2 transduction as an in vivo therapeutic approach--revealed a deleterious effect of bcl-2 transduction.
authors.affiliation: Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia 19104, USA.
authors.forename: P D
authors.initials: PD
authors.lastname: Simon
authors.forename: C K
authors.initials: CK
authors.lastname: Vorwerk
authors.forename: S S
authors.initials: SS
authors.lastname: Mansukani
authors.forename: S J
authors.initials: SJ
authors.lastname: Chen
authors.forename: J M
authors.initials: JM
authors.lastname: Wilson
authors.forename: D
authors.initials: D
authors.lastname: Zurakowski
authors.forename: J
authors.initials: J
authors.lastname: Bennett
authors.forename: E B
authors.initials: EB
authors.lastname: Dreyer
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D000229:Dependovirus; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D005724:Ganglia / Q000166:cytology / Q000187:drug effects*; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics; D016202:N-Methylaspartate / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018690:Excitatory Amino Acid Agonists; D008164:Luminescent Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D049452:Green Fluorescent Proteins; D016202:N-Methylaspartate