There were no significant differences in cell number or apoptotic kinetics within the ganglion cell layer, or in the width of the nerve fiber and plexiform layers between caspase-3
−/− and WT mice at any age. Apoptotic cells were identified by their pyknotic nuclei at the light microscopic level and by positive TUNEL staining. Apart from peripapillary dysplasia, retinal morphology was indistinguishable between WT and caspase-3
−/− retinas at PN0
(Figs. 3A 3B) . As in WT mice, apoptotic nuclei were noted in the ganglion cell layer of caspase-3
−/− mice in the first week after birth (
Fig. 3B , arrows). Abnormal apoptotic kinetics were limited to the inner nuclear layer and were first noted at PN5. Compared with WT mice, in which the thickness of inner and outer nuclear layers was equivalent from PN5 onward
(Fig. 3C) , in caspase-3
−/− mice, the inner nuclear layer at PN5 was slightly thickened and nuclei in the outermost region exhibited heterochromia reminiscent of rod nuclear morphology
(Fig. 3D) . This phenomenon was still present, but was less noticeable by PN13 and resolved at later time points
(Figs. 3F 4A) . In WT retina at PN5, pyknotic TUNEL-positive nuclei were present in the inner nuclear layer
(Fig. 3C) . The number of apoptotic nuclei decreased markedly over the next week, and by PN18, only isolated dying cells were noted
(Fig. 3E 4A) . In contrast, the inner nuclear layer of caspase-3
−/− retina contained fewer apoptotic nuclei than WT retina at PN5
(Figs. 3D 4A) . However, the number of apoptotic nuclei increased over the next week and then declined gradually over the next 2 weeks
(Fig. 4A) . By PN16–18, a moderate number of apoptotic nuclei were still present in the inner nuclear layer
(Figs. 3F 6F) . These were absent by PN23 (data not shown). Therefore, the kinetics of inner nuclear layer apoptosis in the caspase-3
−/− mouse replicated that of WT, but was delayed by 7 to 10 days. Retinal morphology in caspase-3 heterozygous mice was indistinguishable from that of WT mice.