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W. A. Beltran, S. Savina, G. M. Acland, G. D. Aguirre; Retinal Remodeling in a Canine Model of Early Onset Retinitis Pigmentosa. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2984.
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To characterize the retinal morphologic alterations that follow the initiation of photoreceptor cell death in the rcd1 dog, an early onset and rapidly progressive model of RP caused by a mutation in PDE6B.
Retinas from 11 affected rcd1 dogs (2 weeks- 1 year) were used. Retinas from non-affected dogs were used as controls. The tissues were paraformaldehyde fixed and embedded in OCT. Cytologic characteristics of the disease were examined on H&E stained cryosections. TUNEL assay was used to establish the kinetics of photoreceptor cell death. Immunohistochemistry (IHC) using a battery of cell-specific antibodies was used to examine photoreceptors and inner retinal cells.
As previously reported, a rapid decline in photoreceptor cells (rods) was noted resulting in a 50% decrease by 12 weeks of age. TUNEL assay revealed that photoreceptor cell death occurred at all ages (2 weeks- 1 year); however, there was a higher number of labeled cells at 4 and 5 weeks of age. Rod opsin IHC showed the persistence of short rod outer segments up to 9 months of age, yet remodeling of rods evidenced by opsin delocalization, neurite sprouting and neuronal ectopia occurred early. Indeed, these changes were first seen at 4 weeks (opsin delocalization, sprouting) and 7 weeks (ectopia) of age. Cone density was stable until later stages of the disease, at which point some rare figures of cone neurite sprouting were seen. The inner retina appeared to be well preserved throughout the course of the disease, and the most prominent early changes were a retraction of PKCa-IR rod bipolar cell dendrites, and intense GFAP labeling of Müller cells.
Despite a rapid loss of a significant proportion of the rod population early in the disease, there is persistence of rods that maintain their outer segments, prolonged survival of cones, and moderate remodeling of the inner retina. This suggests that the time-window for therapeutic intervention may be wider than previously expected.
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