Abstract
Abstract: :
Purpose: Dark–rearing has been found to slow the rate of retinal degeneration in albino P23H but not S334ter mutant rhodopsin transgenic (Tg) rats (Organisciak et al., 2003). Since eye pigmentation has the same protective slowing effect as dark–rearing in RCS rats (LaVail and Battelle, 1975), we have examined whether eye pigmentation has a comparable slowing effect in the different mutant rhodopsin Tg rats. Methods: Different lines of albino P23H and S334ter Tg rats (on the Sprague–Dawley [SD] background) were bred to Long–Evans (LE) rats to produce pigmented Tg rats. These were compared to albino Tg rats at postnatal days 30, 60, 90 and 120 using the outer nuclear layer (ONL) as a morphological measure of photoreceptor number and ERG a– and b–wave amplitudes as a measure of retinal function. Results: Wild–type pigmented LE rats had virtually identical ONL thicknesses as wild–type SD rats, despite the LE rats having larger ERG a–waves (ANOVA, p<0.01) and b–waves (ANOVA, p<0.01). Pigmented P23H rats had a slower rate of degeneration as measured by ONL thicknesses (ANOVA, p<0.001), greater a–wave amplitudes (ANOVA, p<0.05), and greater b–wave amplitudes (ANOVA, p<0.001) when compared to the albino P23H rats. In contrast, pigmented S334ter rats showed no difference in ONL thicknesses (ANOVA, p>0.05) and ERG a–wave amplitudes (ANOVA, p>0.05) when compared to their albino equivalents. However, b–waves in the pigmented S334ter rats were larger than those from albino S334ter rats (ANOVA, p<0.01). Conclusions: Degeneration of photoreceptors in P23H Tg rats is slowed by eye pigmentation as measured by ONL thickness, while it is not in the S334ter Tg rats. Pigmentation protects functional changes in a– and b–waves for the P23H lines and only the b–waves for the S334ter lines. Since eye pigmentation reduces the level of retinal irradiance, retinas with the P23H rhodopsin mutation are more sensitive to the damaging effects of light than those with the S334ter mutation.
Keywords: retinal degenerations: cell biology • radiation damage: light/UV • transgenics/knock-outs