Fibroblast growth factor-2 decreases hyperoxia-induced photoreceptor cell death in mice

Fibroblast growth factor-2 (FGF2) has neurotrophic effects in vitro and in vivo. It has been demonstrated to decrease photoreceptor cell death in rats exposed to constant light and in rats with an inherited defect in retinal pigmented epithelium (RPE) phagocytosis, but the effects of intravitreous i njections of FGF2 in mice are equivocal. In this study, we used transgenic mice with increased expression of FGF2 in photoreceptors (rhodopsin promote r/FGF2 transgenics) to investigate the effects of sustained increased expre ssion of FGF2 in mice with various types of photoreceptor degeneration, inc luding rd mice that are homozygous for mutated phosphodiesterase beta subun it, Q344ter mice that undergo photoreceptor degeneration because of express ion of mutated rhodopsin, and mice exposed to 75% oxygen for 1 or 2 weeks. At P21, the outer nuclear layer was markedly reduced in rd mice or Q344ter mice regardless of whether they inherited the rbodopsin promoter/FGF2 trans gene. However, after 2 weeks of exposure to 75% oxygen, outer nuclear layer thickness was significantly reduced in littermate control mice compared to FGF2 transgenic mice (P = 0.0001). These data indicate that increased expr ession of FGF2 in photoreceptors protects them from hyperoxia-induced damag e, but does not decrease cell death related to expression of mutated protei ns involved in the phototransduction pathway. This suggests that FGF2 prote cts photoreceptors from oxidative damage, which may play a role in complex genetic diseases such as age-related macular degeneration.