Infection with adeno-associated virus may protect against excitotoxicity.
Gene therapy has developed as a promising approach for therapy in a broad variety of conditions. Viral vectors have been developed that may replace a defective gene, prevent expression of a mutant gene, or deliver a protective gene and thereby delay cellular loss. Using adeno-associated virus containing green fluorescent protein (AAV-GFP) we were able to specifically transduce cells located in the inner retina and induce over-expression of GFP in adult rat retinae. The delivery and expression of GFP had no influence themselves on retinal ganglion cell survival. Administration of the reporter vector AAV-GFP provided retinal ganglion cells with slight but significant protection from intravitreal NMDA. This was a locally mediated phenomenon; greater protection was seen in regions with more transduced cells. Any evaluation of the efficacy of a putative viral vector should consider the possible protective or toxic effect of the native virus.
Dreyer
E B
EB
Department of Ophthalmology, University of Pennsylvania, Scheie Eye Institute, Philadelphia 19104, USA.
Vorwerk
C K
CK
Zurakowski
D
D
Simon
P D
PD
Bennett
J
J
D000818:Animals; D002470:Cell Survival; D000229:Dependovirus / Q000235:genetics*; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D017930:Genes, Reporter / Q000235:genetics*; D005822:Genetic Vectors / Q000235:genetics*; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins / Q000235:genetics; D016202:N-Methylaspartate / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000378:metabolism; D014161:Transduction, Genetic / Q000235:genetics
D018690:Excitatory Amino Acid Agonists; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins; D016202:N-Methylaspartate