Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Apoptosis
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Brain-Derived Neurotrophic Factor / genetics*
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Brain-Derived Neurotrophic Factor / metabolism
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Cell Survival / physiology
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Cytoprotection
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Dependovirus / genetics*
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Excitatory Amino Acid Agonists / toxicity
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Fibroblast Growth Factor 2 / genetics*
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Fibroblast Growth Factor 2 / metabolism
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Gene Expression Regulation / physiology
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Genetic Therapy / methods
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Genetic Vectors
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Green Fluorescent Proteins / genetics
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N-Methylaspartate / toxicity*
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Nerve Crush
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Neuroprotective Agents
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Optic Nerve / pathology
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Rats
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Rats, Sprague-Dawley
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Retinal Diseases / metabolism
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Retinal Diseases / pathology
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Retinal Diseases / prevention & control*
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Retinal Ganglion Cells / drug effects
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Retinal Ganglion Cells / physiology*
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Transfection
Substances
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Brain-Derived Neurotrophic Factor
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Excitatory Amino Acid Agonists
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Neuroprotective Agents
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Fibroblast Growth Factor 2
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Green Fluorescent Proteins
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N-Methylaspartate