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E. M. Scott, G. M. Acland, G. D. Aguirre, W. A. Beltran; Characterization of Photoreceptor Loss and Inner Retinal Remodeling in a Canine Model of Cone-Rod Dystrophy (CRD2). Invest. Ophthalmol. Vis. Sci. 2010;51(13):4063.
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Inherited retinal degenerations (RD) are a frequent cause of blindness sharing a common feature, the degeneration and death of photoreceptor cells. Cone-rod dystrophies (CRD) are a subset of diseases in which cones initially show clinical signs of dysfunction and disease, followed by rods secondarily. This study characterized the kinetics of photoreceptor loss, and evaluated the progression of photoreceptor degeneration and inner retinal remodeling in an early onset canine model of cone-rod dystrophy, (CRD2).
The retinas from four affected and three age-matched non-affected carrier dogs were embedded in OCT, and sectioned at 7 or 10 µm for H&E staining, TUNEL assays and/or immunohistochemistry. The sections extended from the optic nerve to the ora serrata along the superior, inferior, nasal and temporal meridians.
Abnormal morphology of photoreceptors was recognized at 6 weeks of age, the earliest time point examined. Cone outer segments were scarce at 6 weeks and mostly absent by 14 weeks of age. Cone inner segments were stunted and broadened at 6 weeks, and scarcely present by 31 weeks. The proportion of dying photoreceptors, particularly rods, was highest at 6 weeks and reduced by 50% between 14 and 42 weeks of age. Following the early loss of cone outer segments, a decline in the density of both short and medium/long wavelength cone somatas was observed later between 31 and 42 weeks of age. In addition to rod and cone opsin mislocalization, there was also retraction of ON (rod and cone) bipolar cell dendrites in the affected retinas.
CRD2 is an early onset disease characterized by abnormal cone and rod maturation and function followed by the progressive death of rods and secondary structural degeneration of cones. Although both cones and rods are affected, the cone functional and structural abnormalities are more severe. The results suggest a potential time window for cone-directed therapy within the first 31 weeks of life.
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