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


CONCLUSIONS
AAV-mediated delivery of bFGF and BDNF can promote retinal cell survival following excitotoxic insult.
Schuettauf
Frank
F
Department of Ophthalmology, University of Pennsylvania, Scheie Eye Institute, Philadelphia, Pennsylvania, USA. fschuettauf@uni-tuebingen.de
Vorwerk
Christian
C
Naskar
Rita
R
Orlin
Anton
A
Quinto
Kristine
K
Zurakowski
David
D
Dejneka
Nadine S
NS
Klein
Ronald L
RL
Meyer
Edward M
EM
Bennett
Jean
J
D000818:Animals; D017209:Apoptosis; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D002470:Cell Survival / Q000502:physiology; D019610:Cytoprotection; D000229:Dependovirus / Q000235:genetics*; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D016222:Fibroblast Growth Factor 2 / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics; D016202:N-Methylaspartate / Q000633:toxicity*; D009409:Nerve Crush; D018696:Neuroprotective Agents; D009900:Optic Nerve / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012164:Retinal Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000502:physiology*; D014162:Transfection
D019208:Brain-Derived Neurotrophic Factor; D018690:Excitatory Amino Acid Agonists; D018696:Neuroprotective Agents; D016222:Fibroblast Growth Factor 2; D049452:Green Fluorescent Proteins; D016202:N-Methylaspartate