Contrasting effects of FGF on photoreceptor PCD in RDS and rhodopsin mutant mice

Purpose. Photoreceptors of the retinal degeneration slow (rds) mouse fail to form outer segments during histogenesis of the retina whereas those of the transgenic mouse line Ser 6, which express a mutant (Pro347Ser) rhodopsin gene, develop normally. However, both types of photoreceptors subsequently die by programmed cell death (PCD). The goal of this study was to explore the potential survival-promoting activities of fibre blast growth factors (FGF) in photoreceptor PCD. Methods. A single injection of 0.5 μl saline, containing 0.25 μg of basic FGF (FGF-2) or acidic FGF (FGF-1), was given to an anesthetized animal, via a 32-gauge needle, into the vitreous cavity of the right eye. Photoreceptor PCD was identified by the TUNEL method. The left eye of each mouse served as a control in statistical analysis, by the paired two-sample for means t-test, which yielded a P value for the null hypothesis. Results. A single injection of 0.5 μl saline, containing 0.25 μg of FGF-2 or FGF-1, into the vitreous cavity of two-week old Ser 6 mice reduced, on average, the density of TUNEL-positive photoreceptors identifiable in three-week old retinas by approximately 50%; injection of saline alone or IGF-1 had a similar, but smaller, effect (10-20%). These results were statistically significant. The same treatments, in contrast, had no effect on rds mice. No reduction in the density of TUNEL-positive photoreceptors was observed in four-week old Ser 6 mice that had an injection, regardless of the age at which the injection was made (2 weeks or 3 weeks). Conclusions. Our results show that the effects of FGF on Ser 6 mice are specific. There is an early (age 2 weeks) developmental window of a few days, during which FGF may be effective in reducing photoreceptor PCD. The contrasting effects of FGF on Ser 6 and rds mice may suggest that different signal transduction pathways are involved in the mechanisms linking mutation to PCD in these mice. The limited effects of FGF suggest that multiple signal transduction pathways may lead Ser 6 photoreceptors to PCD.

Duke Scholars

Author Fulton Wong Ophthalmology