Intravitreous transplantation of encapsulated fibroblasts secreting the human fibroblast growth factor 2 delays photoreceptor cell degeneration in Royal College of Surgeons rats

We developed an experimental approach with genetically engineered and encap sulated mouse NIH 3T3 fibroblasts to delay the progressive degeneration of photoreceptor cells in dark-eyed Royal College of Surgeons rats. These xeno geneic fibroblasts can survive in 1.5-mm-long microcapsules made of the bio compatible polymer AN69 for at least 90 days under in vitro and in vivo con ditions because of their stable transfection with the gene for the 18-kDa f orm of the human basic fibroblast growth factor (hFGF-2), Furthermore, more , when transferred surgically into the vitreous cavity of 21-day-old Royal College of Surgeons rats, the microencapsulated hFGF-2-secreting fibroblast s provoked a local delay of photoreceptor cell degeneration, as seen at 45 days and 90 days after transplantation. This effect was limited to 2.08 mm( 2) (45 days) and 0.95 mm(2) (90 days) of the retinal surface. In both untre ated eyes and control globes with encapsulated hFGF-2-deficient fibroblasts , the rescued area (of at most 0.08 mm(2)) was significantly smaller at bot h time points. Although, in a few ocular globes, surgical trauma induced a reorganization of the retinal cytoarchitecture, neither microcapsule reject ion nor hFGF-2-mediated tumor formation were detected in any treated eyes. These findings indicate that encapsulated fibroblasts secreting hFGF-2 or p erhaps other agents can be applied as potential therapeutic tools to treat retinal dystrophies.