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Dana Lau, Laura H. McGee, Shangzhen Zhou, Katherine G. Rendahl, William C. Manning, Jaime A. Escobedo, John G. Flannery; Retinal Degeneration Is Slowed in Transgenic Rats by AAV-Mediated Delivery of FGF-2. Invest. Ophthalmol. Vis. Sci. 2000;41(11):3622-3633.
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purpose. 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.
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