Retinal degeneration is slowed in transgenic rats by AAV-mediated delivery of FGF-2.
OBJECTIVE
We evaluated adeno-associated virus (AAV)-mediated gene transfer of basic fibroblast growth factor (FGF-2) as a therapy for photoreceptor degeneration in a transgenic rat model of retinitis pigmentosa.


METHODS
Recombinant adeno-associated virus vector (rAAV) incorporating a constitutive cytomegalovirus (CMV) promoter was used to transfer the bovine FGF-2 gene to photoreceptors. AAV was administered by subretinal injection to transgenic rats (TgN S334ter-4) at postnatal day 15 (P15). Control eyes were uninjected, injected with PBS, or AAV-LacZ. Eyes were examined by histopathology, morphometric analysis, and electroretinography at P60.


RESULTS
Expression of recombinant FGF-2 slowed the rate of photoreceptor degeneration. Morphologic studies demonstrated significantly more photoreceptors surviving in eyes injected with AAV-FGF-2 than in controls. Insignificant rescue effects were seen in retinas injected with buffer only. No significant inflammatory response or neovascularization was detected. Electroretinographic (ERG) responses of eyes injected with AAV-FGF-2 were increased compared with uninjected eyes; however, these amplitudes were not significantly larger than eyes receiving an AAV-LacZ control vector.


CONCLUSIONS
Transduction of retinal cells with AAV-FGF-2 reduces the rate of photoreceptor degeneration in an S334ter-4 animal model. Despite the lack of significantly increased ERG amplitudes from eyes expressing FGF-2, a greater number of surviving photoreceptors was demonstrated. Delivery of FGF-2 using recombinant AAV has potential as a therapy for retinal degeneration.
Lau
D
D
Departments of Molecular Cell Biology and Neuroscience Group, Vision Science, School of Optometry, University of California, Berkeley 94720-2020, USA.
McGee
L H
LH
Zhou
S
S
Rendahl
K G
KG
Manning
W C
WC
Escobedo
J A
JA
Flannery
J G
JG
D000818:Animals; D030801:Animals, Genetically Modified; D003673:Defective Viruses; D000229:Dependovirus / Q000502:physiology*; D004596:Electroretinography; D004797:Enzyme-Linked Immunosorbent Assay; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism / Q000627:therapeutic use*; D019084:Fluorescent Antibody Technique, Indirect; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D008856:Microscopy, Fluorescence; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism / Q000473:pathology / Q000502:physiology / Q000821:virology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012162:Retinal Degeneration / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016222:Fibroblast Growth Factor 2