Basic fibroblast growth factor treatment delays age-related photoreceptor degeneration in Fischer 344 rats

Abstract

This study was undertaken to investigate the potential of basic fibroblast growth factor (bFGF) to delay photoreceptor cell loss in retinas of Fischer 344 rats which exhibit an age-related peripheral retinopathy. Eight male 16-month-old Fischer 344 rats were injected intravitreally with 2.0 micrograms bFGF in the right eye, while the vehicle was injected into the left eye and all rats were killed at two months post-injection. Eight other Fischer rats were injected with either bFGF or vehicle at 16 and again at 18 months, then killed two months later. After enucleation, eyes were processed for light and electron microscopic and morphometric analyses. The distance from the ora serrata to the point where the outer nuclear layer (ONL) in the superior retina was two cells in thickness, called the die-back zone, that represents the extent of the peripheral retinopathy, was compared in bFGF- and vehicle-injected Fischer rats. These measurements revealed that the die-back zone in retinas of eyes injected twice with bFGF was significantly reduced (P < 0.01) when compared to this zone in retinas of age-matched rats that received vehicle injections. However, there was no significant difference (P > 0.05) in this degeneration zone in retinas of 18-month-old rats that received a single-bFGF injection when compared to retinas of respective vehicle-injected rats. In addition, the ONL at 2 and 3 mm from the ora serrata in the superior retina of bFGF-injected 20-month-old Fischer rats was significantly thicker than corresponding regions in retinas of vehicle-control rats. Furthermore, the photoreceptor cells in the superior retina of 20-month-old rats which received two injections of bFGF had normal-appearing inner and outer segments, while the few photoreceptors had short inner and outer segments in vehicle-injected retinas of Fisher rats. These findings reveal that injections of bFGF into eyes of Fischer 344 rats significantly delays the progress of photoreceptor cell degeneration suggesting that exogenous bFGF may act as a survival-promoting factor in these aged retinas.