Abstract
Purpose: :
To investigate the changes that occur in retinal neurons of dogs with an advanced retinal degeneration due to a PDE6A null mutation.
Methods: :
The posterior eye cups from PDE6A mutant dogs and normal controls were processed for immunohistochemistry and stained with a variety of antibodies to identify different neuron types.
Results: :
Canine rods stained with the anti–opsin antibody RET–P1. Surprisingly RET–P1 immunoreactive (IR) cell bodies persisted in the outer retina of dogs with advanced retinal degeneration. These IR cells showed some sprouting of neurites, predominantly in a horizontal direction. Anti–cone arrestin antibody stained most of the remaining cell bodies in the region of the residual outer nuclear layer (ONL) of dogs with advanced degeneration. These cells had processes which ramified within the ONL. Rod bipolar cells stained with PKCα showed a ramification of cell processes within the outer plexiform layer. Displaced rod bipolar cell were present in both the residual ONL and ganglion cell layer. The cell bodies of horizontal cells stained with an anti–calbindin antibody appeared hypertrophied. GFAP staining revealed hyperactivity of Müller cells throughout the thickness of the remaining retina.
Conclusions: :
This study revealed that similar to other retinal dystrophy models previously investigated, there was evidence of retinal remodeling in the PDE6A mutant dog. Despite the apparent rapid loss of rods in this model some cells that were IR to anti–opsin antibody remained in the later stages of the disease. Cones persisted longer, although like the rods they had lost their inner and outer segments. The surviving photoreceptor cell bodies tended to sprout processes in a horizontal direction. In contrast, sprouting from cone cell bodies occurred from outer to inner retina in earlier stages of the degeneration. The inner retina also showed evidence of remodeling, with displacement of bipolar cells, sprouting of cell processes in a disorganized fashion and evidence of hypertrophy of horizontal cells.
Keywords: retinal degenerations: hereditary • immunohistochemistry • retina