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

American Staffordshire Terriers (ASTs) with a c.296G>A variant in <i>ARSG</i> develop progressive ataxia, cerebellar atrophy, and neuronal accumulation of autofluorescent storage material. Human subjects with <i>ARSG</i> variants exhibit hearing loss and rod-cone dystrophy without apparent other neurological involvement and <i>arsg</i> knockout mice exhibit progressive ataxia, lysosomal storage, and photoreceptor loss. Owners of 8 of 11 affected ASTs evaluated for the <i>ARSG</i> risk variant reported observing visual impairment in their dogs, suggesting that the canine disease may involve retinal dysfunction consistent with human subjects and mice with <i>ARSG</i> variants. To assess whether this might be the case, electroretinography was performed on four affected and three unaffected ASTs. Three affected dogs that were exhibiting signs of ataxia had attenuated electroretinogram (ERG) amplitudes indicative of rod and cone photoreceptor dysfunction, while ERG responses were not attenuated in a younger dog that had not yet shown signs of ataxia or visual impairment. Autofluorescent inclusions were observed in the retinal pigment epithelium and retinal ganglion cell layer of two affected dogs that were euthanized due to neurological disease progression. The results from these cases indicate that standardized electroretinography can be used to detect retinal dysfunction in dogs with the <i>ARSG</i>-related disorder and in other disorders in which dogs exhibit apparent impairment in visually mediated behavior.