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G.M. Acland, S.E. Pearce–Kelling, A.M. Komáromy, G.D. Aguirre; Three Canine Cone–rod Dystrophies . Invest. Ophthalmol. Vis. Sci. 2004;45(13):3587.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Cone–rod dystrophies are severe hereditary retinal diseases characterized by degeneration of cone photoreceptors preceding that of rods. At least 15 mapped human loci are recognized, including at least 9 identified causative genes (ABCA4, CRX, GUCA1A, UNC119, GUCY2D, RDS/peripherin, RIM1, RDH5 and RPGR). Until now most well characterized canine hereditary retinal degenerations have been rod–cone disorders, in which rod disease precedes that of cones. We now report 3 distinctly different canine cone rod dystrophies identified in the American Staffordshire Terrier, the American Pit Bull Terrier, and the Glen of Imaal Terrier breeds. Methods: Each disease was initially recognized clinically in privately owned dogs from the respective breeds. To facilitate genetic investigation, experimental pedigrees were developed by breeding affected dogs to research colony dogs of known genetic and phenotypic history. Retinal function was evaluated by clinical electroretinography. Morphologic studies were conducted on fixed retinas of affected dogs. Results: Because the retinal disorders in these 3 strains of dog are all cone rod dystrophies, but exhibit marked disorder–specific differences in age of onset and rate of progression of disease, the diseases are identified as CRD1, CRD2, and CRD3. Crossbreedings between CRD1 and CRD2 affected dogs established that these two diseases are not allelic. In CRD1, severe cone and rod dysfunction are present in ERGs of very young pups; in CRD2 cone dysfunction is similarly severe, but rod dysfunction is initially less so. In both CRD1 and CRD2 retinal degeneration proceeds rapidly and is esssentially endstage by one year postnatal. In CRD3 retinal function is initially normal, but cone dysfunction is detectable by ERG at approximately 1 year of age and cone and rod function slowly deteriorate from then on. Cone abnormalities are morphologically apparent in CRD3 affected retina at 7 months of age. Conclusions:These 3 diseases offer promise both as novel large animal natural models of human cone–rod dystrophies, and as opportunities to evaluate potential therapies for cone degenerative disorders. Candidate gene analysis is currently underway to identify the causative genes or as a prelude to genome wide screens, if necessary.
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