ABSENCE OF P53 DELAYS APOPTOTIC PHOTORECEPTOR CELL-DEATH IN THE RDS MOUSE

Purpose. This study was aimed at determining whether or not apoptotic photoreceptor cell death in a mouse model of inherited retinal degener ation is p53 dependent. Methods. A colony of p53-deficient rds mice we re obtained by crossing homozygous rds mice with animals homozygous fo r a targeted disruption of the p53 gene and genotyping the offspring o f the Fl cross. Both parental strains were on a BALB/c background. Age matched p53-deficient rds mice and controls (p53-deficient, rds and B ALB/c mice), were sacrificed from day 1 to day 58 after birth. Eyes we re paraffin-embedded and a modified terminal dUTP nick-end labeling (T UNEL) technique was used to detect the number of cells displaying DNA fragmentation within the sectioned retina. Eyes were also resin-embedd ed for semi-thin and ultra-thin sectioning. Results. The peak in photo receptor apoptosis, which occurs at 16 days in the rds mouse, was dela yed by 3 days in p53-deficient rds mice. In addition, there was also a delay in the loss of photoreceptor cells between 16 and 26 days. Howe ver, absence of p53 did not prevent retinal degeneration in the rds mo use. The number of photoreceptor cells in p53-deficient rds mice at 35 days was very similar to that in the controls. Conclusions. We have d emonstrated that absence of p53 delays but does not prevent photorecep tor cell loss in the rds mouse. Our results provide evidence for plast icity in the mechanism by which apoptosis proceeds in retinal degenera tion.