Adeno-associated viruses containing bFGF or BDNF are neuroprotective against excitotoxicity

Purpose. Brain-derived neurotrophic factor (BDNF) and basic fibroblast growth factor (bFGF) hold much promise for the protection of retinal ganglion cells against excitotoxic cell death. We tested the possibility of delivering these growth factors to retinal ganglion cells via an adeno-associated vi...

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Bibliographic Details
Published in:Current eye research 2004-12, Vol.29 (6), p.379-386
Main Authors: Schuettauf, Frank, Vorwerk, Christian, Naskar, Rita, Orlin, Anton, Quinto, Kristine, Zurakowski, David, Dejneka, Nadine S., Klein, Ronald L., Meyer, Edward M., Bennett, Jean
Format: Article
Language:English
Subjects:
adeno-associated virus
Animals
Apoptosis
basic fibroblast growth factor
brain-derived neurotrophic factor
Brain-Derived Neurotrophic Factor - genetics
Brain-Derived Neurotrophic Factor - metabolism
Cell Survival - physiology
Cytoprotection
Dependovirus - genetics
Excitatory Amino Acid Agonists - toxicity
excitotoxicity
Fibroblast Growth Factor 2 - genetics
Fibroblast Growth Factor 2 - metabolism
Gene Expression Regulation - physiology
Genetic Therapy - methods
Genetic Vectors
Green Fluorescent Proteins - genetics
N-Methylaspartate - toxicity
Nerve Crush
Neuroprotective Agents
Optic Nerve - pathology
Rats
Rats, Sprague-Dawley
Retinal Diseases - metabolism
Retinal Diseases - pathology
Retinal Diseases - prevention & control
retinal ganglion cells
Retinal Ganglion Cells - drug effects
Retinal Ganglion Cells - physiology
Transfection
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Summary:Purpose. Brain-derived neurotrophic factor (BDNF) and basic fibroblast growth factor (bFGF) hold much promise for the protection of retinal ganglion cells against excitotoxic cell death. We tested the possibility of delivering these growth factors to retinal ganglion cells via an adeno-associated viral (AAV) vector and tested their efficacy in two models of excitotoxicity. Methods. Rat retinas were infected with AAV vectors encoding bFGF or BDNF. A control vector containing green fluorescent protein (GFP) was injected in the contralateral eye. Eyes were subjected to either an intravitreal injection of N-methyl-D-aspartate (NMDA) or optic nerve crush, and ganglion cell survival was evaluated. Results. AAV.CMV.bFGF and AAV.CBA.BDNF were neuroprotective against NMDA injection 1 month post-treatment. Additionally, AAV.CMV.bFGF was protective against optic nerve crush. Conclusion. AAV-mediated delivery of bFGF and BDNF can promote retinal cell survival following excitotoxic insult.
ISSN:0271-3683
1460-2202
DOI:10.1080/02713680490517872