Lau D, McGee L H, Zhou S, Rendahl K G, Manning W C, Escobedo J A, Flannery J G
Departments of Molecular Cell Biology and Neuroscience Group, Vision Science, School of Optometry, University of California, Berkeley 94720-2020, USA.
Invest Ophthalmol Vis Sci. 2000 Oct;41(11):3622-33.
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.
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.
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.
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.
我们评估了腺相关病毒（AAV）介导的碱性成纤维细胞生长因子（FGF - 2）基因转移作为治疗视网膜色素变性转基因大鼠模型中光感受器退化的一种疗法。
使用包含组成型巨细胞病毒（CMV）启动子的重组腺相关病毒载体（rAAV）将牛FGF - 2基因转移至光感受器。在出生后第15天（P15）通过视网膜下注射将AAV给予转基因大鼠（TgN S334ter - 4）。对照眼未注射、注射磷酸盐缓冲液（PBS）或AAV - LacZ。在P60时通过组织病理学、形态计量分析和视网膜电图检查眼睛。
重组FGF - 2的表达减缓了光感受器退化的速率。形态学研究表明，注射AAV - FGF - 2的眼中存活的光感受器明显多于对照组。仅注射缓冲液的视网膜中观察到不显著的挽救效果。未检测到明显的炎症反应或新生血管形成。与未注射的眼睛相比，注射AAV - FGF - 2的眼睛的视网膜电图（ERG）反应有所增加；然而，这些振幅并不显著大于接受AAV - LacZ对照载体的眼睛。
用AAV - FGF - 2转导视网膜细胞可降低S334ter - 4动物模型中光感受器退化的速率。尽管表达FGF - 2的眼睛的ERG振幅没有显著增加，但证明有更多存活的光感受器。使用重组AAV递送FGF - 2有作为视网膜变性疗法的潜力。
