PRCD-associated retinitis pigmentosa in dogs and humans

PRCD is a ∼6 kDa protein localized to the cytosolic surface of rod and cone outer segment discs. Pathogenic variants in the PRCD gene cause autosomal recessive retinal degeneration in human patients and in over 65 dog breeds. We characterized the natural history and phenotype of PRCD-associated retinal disease in dogs and compared it with the human condition. Human patients with PRCD-associated retinitis pigmentosa, p.R22∗ variant, exhibited severe, retina-wide degeneration, abnormal electroretinograms, and constricted visual fields. However, visual acuity and foveal photoreceptor structure could be preserved into the second decade of life. In dogs, four homozygous mutants (p.Cys2Tyr variant, PRCD^Mis/Mis), one heterozygous, and 24 wild-type dogs were evaluated from 0.4 to 4.8 years of age using serial in-vivo imaging modalities, complemented by histological quantification, Western blotting, and immunohistochemistry. OCT revealed significant outer nuclear layer (ONL) thinning in all quadrants by 0.8 year, with the fovea-like region (FLR) spared until 2.3 years in PRCD^Mis/Mis dogs. The inferior retina showed the most severe thinning, with 92% loss by 4.8 years, whereas the cone-rich visual streak and FLR showed 22% loss by 4.8 years. Scotopic a-wave ffERG amplitudes were significantly reduced at all time points, while photopic responses remained stable. At early stages of disease, the preferential involvement of the inferior quadrant was confirmed by histology. Western blot and immunostaining confirmed absence of PRCD protein in mutant retinas. Together, these findings demonstrate a rod-dominant degeneration with a distinct spatial pattern and relative central preservation, closely mirroring the human phenotype.