Genetic basis - Caused by a 4-base pair deletion (c.487_490delAAGA) in exon 5 of the RPE65 gene. This deletion causes a frameshift mutation resulting in a premature stop codon and a truncated, non-functional RPE65 protein. RPE65 is critical for the visual cycle, assisting in the regeneration of visual pigments in the retinal pigment epithelium. The inheritance pattern is autosomal recessive, requiring two copies of the defective gene for disease manifestation.
Pathophysiology - Mutation leads to disrupted retinal pigment epithelium function. Impaired regeneration of 11-cis-retinal in photoreceptors, especially affecting rod photoreceptors. Causes congenital night blindness characterized by impaired rod function but preserved cone function.
Clinical Features - Night vision impairment from early life. Dogs may exhibit difficulty seeing in dim light or darkness but have normal or near-normal daylight vision. Retinal degeneration can be slow-progressing. Early fundoscopic changes may not be visible. Electroretinography (ERG) shows absence of rod responses.
Diagnosis - Clinical history and ophthalmic exam. Electroretinography demonstrating rod dysfunction. Confirmatory genetic testing for the RPE65 deletion.
Treatment - Currently, there is no cure. Gene therapy in canine models targeting RPE65 defects shows promise for future treatments.
Why This Matters to Breeders and Vets - Breeders: Genetic screening assists in eliminating carriers from breeding programs, reducing disease prevalence. Vets: Early diagnosis informs management and prevents misdiagnosis of other retinal diseases.