Abstract
Purpose: :
To examine the changes in the outer retina, their synaptic connectivity and the location and rate of apoptotic cells in S334 ter line–3 and line–5 and RCS rats.
Methods: :
Eight dystrophics RCS rats (rdy+p–) and eight S334 ter–line 3 and eight line–5 at P11–13, P30, P60, P90 and two congenic non–dystrophic RCS rats (rdy–p–) at P30 as controls, were studied anatomically by immunohistochemistry for various cell and synaptic markers, and by TUNEL label.
Results: :
S334 ter line–3 exhibited the fastest rate of degeneration with an early loss of photoreceptors, with two layers remaining at P30. At P60 and P90, both S334 ter lines showed only cones at the ONL. In S334 ter rats, bipolar cells showed a retraction of their dendrites forming clusters along the OPL. In the RCS rats, sprouting of the bipolar and horizontal cell dendrites into the debris zone could be seen at P60. In S334 ter rats, horizontal cell dendrites were diminished at P13, showing gaps in the OPL at P60. At P90 almost no dendritic terminals could be seen. The apoptosis rate was different in both S334 ter lines and RCS rats. RCS rats showed significant apoptosis in ONL at P 30, affecting all levels of the ONL. S334 ter line–3 rats showed a significant number of photoreceptors affected at P11, occupying the innermost part of the ONL. Line–5 showed a lower number of apoptotic cells within the same location.
Conclusions: :
The S334 ter line–3 rat has a faster progression of degeneration than line–5 and RCS. The horizontal and bipolar terminals are already affected at P11–P13 in all models. The anatomic differences between the two types of rats are related to the appearance of the debris zone; RCS rats show a sprouting of horizontal and bipolar cell dendrites that it is not found in the S334 ter rats. The apoptosis rate is related with the mechanism of the degeneration; in the rhodopsin mutation rats (S334 ter rats) the first photoreceptor cells affected are those more exposed to light close to the OPL; in the RCS rats, in which the degeneration is a primary defect of the RPE, the cells were affected with no selective location in the outer nuclear layer.
Keywords: retinal degenerations: cell biology • retina: distal (photoreceptors, horizontal cells, bipolar cells) • apoptosis/cell death