APOPTOSIS LEADS TO PHOTORECEPTOR DEGENERATION IN INHERITED RETINAL DYSTROPHY OF RCS RATS

Purpose. To determine the pathogenetic mechanism of photoreceptor cell degeneration in the inherited retinal dystrophy in Royal College of S urgeons (RCS) rats. Methods. The dystrophic retinas of the pink-eyed R CS (RCS-rdy-p) rats were examined for DNA fragmentation by agarose gel electrophoresis of retinal DNA and by TdT-mediated bio-tin-dUDP nick- end labeling (TUNEL) in paraffin sections. Rats ranging in age from 3 to 60 days were examined. Results. Agarose gel electrophoresis of reti nal DNA isolated from animals 25, 30, 35, and 40 days Old showed a lad der pattern of degradation with bands corresponding to multiples of 18 0 to 200 base pair subunits. TUNEL study showed increasing labeling of photoreceptor cells with progression of the retinal dystrophy of the RCS rats. Conclusions. Apoptosis is the dominant mechanism of photorec eptor degeneration in the RCS rat, which has a genetic defect in the p hagocytic activity of retinal pigment epithelium. The onset of the deg eneration appeared to vary between rod cells in the different regions of the eye.