Retinal degeneration is slowed in transgenic rats by AAV-mediated deliveryof FGF-2

PURPOSE. We evaluated adeno-associated virus (AAV)-mediated gene transfer o f basic fibroblast growth factor (FGF-2) as a therapy for photoreceptor deg eneration in a transgenic rat model of retinitis pigmentosa. METHODS. Recombinant adeno-associated virus vector (rAAV) incorporating a c onstitutive 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 hist opathology, morphometric analysis, and electroretinography at P60. RESULTS. Expression of recombinant FGF-2 slowed the rate of photoreceptor d egeneration. Morphologic studies demonstrated significantly. more photorece ptors surviving in eyes infected with AAV-FGF-2 than in controls. Insignifi cant rescue effects were seen in retinas injected with buffer only. No sign ificant inflammatory response or neovascularization was detected. Electrore tinographic (ERG) responses of eyes injected with AAV-FGF-2 were increased compared with uninjected eyes; however, these amplitudes were not significa ntly 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 lac k of significantly increased ERG amplitudes from eyes expressing FGF-2, a g reater number of surviving photoreceptors was demonstrated. Delivery of FGF -2 using recombinant AAV has potential as a therapy for retinal degeneratio n.