title: Adeno-associated viruses containing bFGF or BDNF are neuroprotective against excitotoxicity.
abstract: 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.
authors.affiliation: Department of Ophthalmology, University of Pennsylvania, Scheie Eye Institute, Philadelphia, Pennsylvania, USA. fschuettauf@uni-tuebingen.de
authors.forename: Frank
authors.initials: F
authors.lastname: Schuettauf
authors.forename: Christian
authors.initials: C
authors.lastname: Vorwerk
authors.forename: Rita
authors.initials: R
authors.lastname: Naskar
authors.forename: Anton
authors.initials: A
authors.lastname: Orlin
authors.forename: Kristine
authors.initials: K
authors.lastname: Quinto
authors.forename: David
authors.initials: D
authors.lastname: Zurakowski
authors.forename: Nadine S
authors.initials: NS
authors.lastname: Dejneka
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Klein
authors.forename: Edward M
authors.initials: EM
authors.lastname: Meyer
authors.forename: Jean
authors.initials: J
authors.lastname: Bennett
mesh_terms: 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
chemical_list: 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