Adenovirally expressed basic fibroblast growth factor rescues photoreceptor cells in RCS rats

PURPOSE. To evaluate the abilities of recombinant adenovirus carrying the b asic fibroblast growth factor (bFGF) gene to (1) produce bFGF protein in vi tro and (2) rescue retinal photoreceptors in Royal College of Surgeons (RCS ) rats in vivo. METHODS. Cultured human retinal pigment epithelial cells were infected with one of the following two replication-deficient adenoviral vectors that dri ve inserted genes by p-actin promoter with cytomegalovirus enhancer: AxCAJS bFGF, which expresses the human bFGF gene, and AxCAlacZ, carrying the cDNA of bacterial beta-galactosidase as a viral control. These viruses and recom binant bFGF protein were also injected into the subretinal space of RCS rat s at the age of 21 days. The production of bFGF was evaluated by an immunoh istochemical method in vitro and in vivo. The secretion of bFGF produced in vitro was quantified by an enzyme-linked immunosorbent assay. The thicknes s of the outer nuclear layer (ONL) as a marker of photoreceptor cell rescue was estimated at 2, 28, and 56 days after the injections. RESULTS. AxCAJSbFGF produced human bFGF protein effectively both in vitro a nd in vivo. The semiquantitative analysis of ONL thickness revealed a signi ficant protective effect of AxCAJSbFGF and the recombinant bFGF protein inj ection up to 56 days after injection. CONCLUSIONS. These results demonstrate that a recombinant adenoviral vector can achieve the transfer of bFGF gene in vitro and have a protective effec t for photoreceptor cells in vivo. Gene therapy with a bFGF-expressing reco mbinant adenoviral vector may provide a new strategy with which to target r etinal degenerative diseases.