New collaborative research by US and Finnish scientists, published in the open access journal PLoS (PLoS ONE 9(9): e106610. doi:10.1371/journal.pone.0106610), has described a new canine retinal pathology not previously detected in other well-studied models of retinal degeneration. The phenotypic heterogeneity in the newly uncovered retinal degeneration recorded by the researchers is not unlike the clinical heterogeneity found in human retinitis pigmentosa and other retinal degenerations. As such, the research may provide a useful large animal model to study the pathophysiology of a retinal atrophy and investigate new therapeutic opportunities to interfere with the course of the disease.
The research team behind the work examined 324 Swedish vallhund dogs, which physically resemble the German Sheperd breed although of a much shorter stature. The researchers were able to describe a unique form of retinopathy characterized by a multifocal appearance of red and brown discoloration of the tapetal fundus followed over time by retinal thinning. In all, 113 of the 324 dogs had a clinical phenotype consistent with retinopathy resulting in an estimated prevalence of 34.9% Analysis of the data collected indicated that the retinopathy could be divided into three distinct stages based on clinical severity. In stage 1, the mildest stage with no signs of vision loss, a diffuse multifocal red or brown discoloration of the tapetal fundus could be observed in 34 of the animals with a mean age of 4.3 ±3.7 years. However, such clinical features could occur as early as 1.9 years or as late as 17.8 years. In Stage 2, the first signs of retinal degeneration were exhibited characterised by multifocal, geographic thinning, at first in the periphery and then spreading throughout the tapetal fundus. The owners of dogs at this stage reported mild to moderate signs of night-blindness in their dogs. In the final phase, stage 3 disease, more diffuse retinal thinning could be observed with a significant loss of night-vision and severely impaired day-vision, sometimes to the point of complete blindness. In their publication the researchers state that, “This appears to be a new retinal disease phenotype which appears to be breed specific since we are not aware of the presence of a similar disease phenotype in other dog breeds”.
Due to similar anatomies and the presence of a cone photoreceptor rich central region, canine retinal disease models are perfectly suited to contribute significant understanding of the mechanisms of disease and the potential for new therapies in human populations. One of the more interesting aspects in the current research was that significant clinical heterogenity found among many of the dogs, including sibs with dramatically different phenotypes. One example highlighted a single animal with the disorder examined until almost 18 years of age but never progressed beyond Stage 1. Despite the variability in the age of onset, coupled with incomplete pedigree information, the researchers hypothesized from the available data that an autosomal recessive pattern of transmission appeared to be the most plausible mode of inheritance, including the observation that “affected animals can originate from the breeding of non-affected dogs”.