The pearl mutation accelerates the schedule of natural cell death in the early postnatal retina

Abstract

The time of maximal occurrence of pyknotic nuclei in the retinal ganglion cell layer of postnatal pearl mutant mice is earlier than that in normal mice (Linden and Pinto 1985). Both ganglion and displaced amacrine cells and glia populate the ganglion cell layer. Thus, in order to show that ganglion cells themselves are affected, we counted the numbers of surviving axons in the optic nerve of postnatal day (PND) 0, 4, 12 and adult mice. On PND 0, pearl mutant mice had 139,000 +/- 2800 (SEM) optic axons, about 8% more than wild-type mice (128,000 +/- 1,700; p = 0.031) but on PND 4, pearl mutants had 24% fewer axons than wild-type mice (96,000 +/- 3700 and 119,000 +/- 4600, respectively; p = 0.008). Thus, pearl mutants lose nearly five times as many retinal ganglion cells as wild-type mice in the interval from PND 0 to 4. The number of axons present in adult mice was nearly equal (56,700 +/- 3200 for wild-type and 52,500 +/- 2700 for pearl mutants p = 0.37). We searched for evidence for changes in the schedule of cell death among other neurons of the retina by counting the number of pyknotic nuclei in the various retinal layers. On PND 4, pearl mutant mice had more pyknotic nuclei in the neuroblastic layer than wild-type mice (5000 +/- 400 and 3900 +/- 300, respectively; p less than 0.05). The time-course of the appearance of pyknotic nuclei in the outer nuclear layer differed for the two genotypes (ANOVA, F = 12.5, p less than 0.001). The most striking difference was a greater number of pyknotic nuclei on PND 20 for the pearl mutants (1300) than for wild-type (480; p = 0.002). However, the total number of photoreceptors in adults did not differ between the two genotypes (3.6 x 10(6) +/- 2.4 x 10(5) for wild-type and 3.7 x 10(6) +/- 3.3 x 10(5) for pearl; p greater than 0.8). These results, taken together, show that natural cell death occurs at an earlier time for retinal ganglion cells of pearl mutants, but that the total number of retinal neurons surviving to adulthood is not affected appreciably by the mutation.