between Pigmented and Albino Rats
subdivision 1 or to subdivision 2 as have been defined in this study Similarly,
it is unclear whether the description ‘inner part o f the ONL’ described by Carter-Dawson and LaVail refers to subdivision 3 or to subdivision 4 in the present study.
4.3.2 Spatial patterns o f cell generation in pism ented and albino rats
In both the pigmented and albino animals the pattern of thymidine labelling in all three retinal layers examined followed a similar centre to periphery gradient
as reported for other normally pigmented rodents (Drager, 1985; Reese and Collelo, 1992). In other words, cells tended to withdraw from the cell cycle earlier in central than in peripheral locations. In the cat, there is evidence that
this centre to periphery gradient is centred on the area centralis (Walsh and Polley, 1985). However, the results o f this study indicate that the optic nerve head may prove to be the nodal point in the rat. The only marked difference was a gradually increasing delay in these patterns in albinos from approximately PCD 14.
In the GCL, although the different cell types have not been distinguished in this layer, the finding that there are differences in patterns o f cell production
between pigmented and albino animals may be able to elucidate the chiasmatic problem in albino animals. In rodents, there is evidence that at defined
locations in the temporal retina, ganglion cells destined to project ipsilaterally
are generated earlier than those from the same region that will project
contralaterally (Drager, 1985; Reese and Collelo, 1992). The results reported in
this study do not resolve the issue of why chiasmatic pathways are
systematically disrupted in albinos. Unfortunately, rodents are a poor model in
which to address the question of birth dates in relation to chiasmatic pathways, as cells that give rise to the two projections totally overlap in the temporal retina with the majority of them giving rise to a crossed projection (Jeffery et ah,
1981). Therefore, it is not possible to tell in the albino which cells form the normal crossed projection and which give rise to the aberrant pathway. Despite this, it is interesting that the 2-3 day difference in birth dates between cells in the temporal retina that give rise to the uncrossed pathway and then the crossed
projections (Drager, 1985; Reese and Collelo, 1992) is similar in magnitude to the temporal lag in cell production observed between the strains in this chapter.
Delayed patterns o f neurogenesis in the albinos throughout the retinal layers imply that retinal progenitors may have failed to receive commitment signals
from earlier-bom cells or from cells that they already have differentiated at the time that they should normally leave the cell cycle, differentiate and determine their cell fates. In support of this, Altshuler et al. (1991) have speculated that the first cells to be bom, which have either just decided to exit the cell cycle or
they are newly postmitotic, are able to commit to a cell fate. The first cells to exit the cell cycle follow a default pathway which is likely to be occupied by the first-born ganglion cells. These first-born cells could make inductive factors
that induce one, or more than one, o f the next cell types to be bom (Tumer and
Cepko, 1987; Tumer et al., 1990). In the rat these are cones, horizontal cells, or
amacrine cells (Braekevelt and Hollenberg, 1970). At the final period o f neurogenesis, cells that are sensitive to commitment encounter an environment
that is not as uniform as for the earlier stages of neurogenesis. That is to say,
result of inducers produced by early bom cells and/or due to changes in the potential of the progenitors that occur as development proceeds (Altshuler et al.,
1991). For example, culture systems in which rat photoreceptor progenitors from about PCD 21 (rod generation is maximal) and PCD 15 (rod generation is minimal) were aggregated, demonstrated that when PCD 15 cells were cultured with a 50x excess o f PCD 21 cells, the rate of rod production in the former cells was 55-fold higher than when cultured without PCD 21 cells (Wattanabe and Raff, 1990). This means that cell-cell interactions are required for rod determination and/or differentiation.
It is not clear how alterations in patterns of cell production found in the albino
throughout the retinal layers could result in the two other deficits present in hypopigmented mammals: a cell specific reduction in rod numbers (Jeffery and Kinsella, 1992) and an underdeveloped central retina (Stone et al., 1978). It is clear that the relative delay in patterns of cell production is more marked in rather later developmental stages than earlier stages, being particularly apparent
around PCD 19. Retinal cells are generated in two overlapping phases. The first includes ganglion cells, amacrine cells, horizontal cells and cones. The
second includes the majority of cells in the neural retina including bipolar cells and rods (Harman and Beazley, 1989). Hence it is likely that the temporal focus
of the disruption is towards the second phase, which will include rods that are
known to be specifically affected in albinos (Jeffery et al., 1994). Furthermore,
deficits found in the ONL as a result of excessive mitosis during the period of rod generation are not only reflected in a delay in the centre to periphery
gradient of cell production but also in the distribution of thymidine -labelled
cells through the four subdivisions of the ONL (Chapter 4). There is evidence that patterns of cell addition follow a gradient in pigmented animals (Carter- Dawson and LaVail, 1979), however the results reported in this study revealed a disruption to this pattern in albinos originating at PCD 17-PCD 19 which is the time of peak rod production (Chapter 4 Fig. 27). Hence, excessive cell
production and cell death seem to be linked with reduced rod numbers in
albinos (Jeffery et ah, 1994a; Jeffery et ah, 1997) and a disruption in the normal spatial distribution o f these cells through the depth o f the ONL.