Retinal Function Deficits in American Staffordshire Terriers with a Late-Onset Neurodegenerative Disease Associated with an ARSG Variant

American Staffordshire Terriers (AST) with a c.296G>A variant in ARSG develop progres-sive ataxia, cerebellar atrophy, and neuronal accumulation of autofluorescent storage ma-terial. Human subjects with ARSG variants exhibit hearing loss and rod-cone dystrophy without apparent neurological involvement and arsg knock-out mice exhibit progressive ataxia, lysosomal storage and photoreceptor loss. A study was undertaken to determine whether ASTs homozygous for the c.296G>A variant exhibit retinal dysfunction con-sistent with human subjects and mice with ARSG variants. Owners of 8 of 11 affected ASTs reported observing late-onset visual impairment in their dogs. Affected dogs that were exhibiting signs of ataxia had attenuated electroretinogram (ERG) amplitudes indic-ative of rod and cone photoreceptor dysfunction, while ERG responses were not attenuat-ed in a younger dog that had not yet shown signs of ataxia or visual impairment. Auto-fluorescent inclusions were observed in the retinal pigment epithelium and retinal gan-glion cell layer of two affected dogs that were euthanized due to neurological disease pro-gression. These results indicate that while the disease phenotype varies between humans, mice and dogs with ARSG variants, progressive photoreceptor dysfunction is a consistent feature in all 3 species.