Because of the uniform distribution and rate of disease along the superior and inferior meridians, we determined cell death by using TUNEL assays in sections from the superior meridian. The earliest age when cell death was examined by TUNEL assay was 3.9 weeks, because this was the age when the first morphologic signs of disease were detected. Approximately 31 to 48 TUNEL-labeled cells per 1 M μm
2 of ONL were counted. The proportion of photoreceptors undergoing cell death was higher at 5 and 6 weeks, and reached a peak of more than 300 TUNEL-positive cells per 1 M μm
2 of ONL at 6.7 weeks of age. In normal retinas of 4, 5, and 6 week-old beagles, the number of TUNEL-positive cells per unit area of ONL was significantly lower and did not exceed six per 1 M μm
2 of ONL. At 8 weeks of age, the proportion of photoreceptors undergoing cell death in the mutant retina had decreased to approximately half that occurring at 6.7 weeks (∼150 TUNEL-positive cells per 1 M μm
2 of ONL). At any given time after 12 weeks of age, the proportion of dying photoreceptors was significantly reduced and close to 80 cells/1 M μm
2 of ONL
(Fig. 3) . TUNEL-labeled cells were equally distributed throughout the length of the retina, but it appeared that at the earlier ages, there were more dying cells located in the vitreous half of the ONL
(Fig. 4A1) . Yet, although, TUNEL-positive photoreceptors were seen in the outer half of the ONL, it was extremely rare before 26 weeks of age to detect any labeling in the outermost row of ONL nuclei, where cone somas are located
(Figs. 4A1 4A2) . In 26- and 40.6-week-old
XLPRA2 retinas, it was frequent to observe, particularly in the retinal periphery, cone nuclei that were ectopically located in the IS
(Fig. 4A3) . Double fluorescence labeling showed that a few displaced cone nuclei were TUNEL positive
(Fig. 4A4) . Rare TUNEL-positive cells were also present in the INL and GCL in both mutant and normal young retinas (4–6 weeks), and this was therefore considered to be a normal finding not associated with disease. At later time points in the mutants, there was a relative absence of TUNEL-labeling in those layers.