New canine study can benefit diagnostics and treatment of retinitis pigmentosa

By Emily Henderson, B.Sc.Mar 11 2020

A study performed on canines at the University of Helsinki characterizes a gene variant in the regulatory region of the retina that causes abnormal functioning of retinal genes and, ultimately, leads to loss of vision in dogs.

Miniature Schnauzers suffer from progressive retinal atrophy (PRA), which results in complete loss of vision of the dog. Image Credit: Pixabay.

The study could be useful in the diagnostics and treatment of retinitis pigmentosa—a disease that affects two million people across the world.

For now, changes in the regulatory regions of genes as causes of disease are relatively poorly known. In fact, our recently published study offers, in addition to diagnostics, a valuable model for understanding the biology of the retina and associated disease.”

Hannes Lohi, Study Lead and Professor, University of Helsinki

Since the 1990s, there have been worldwide efforts to determine the genetic cause of retinal atrophy in Miniature Schnauzers.

This breed is affected by progressive retinal atrophy (PRA), which causes a complete loss of vision. Lohi’s team found several dogs of the same pedigree in the process of losing their vision, indicating that it is a hereditary disease.

We started compiling research data by comparing eye examination statements, quickly suspecting that more than one form of the disease occurred in the breed. This was an observation central to the progress of the project.”

Maria Kaukonen, DVM, Study Principal Author and Postdoctoral Researcher, University of Helsinki

Depending on the symptoms, the scientists classified the dogs into two groups. Subsequent gene analyses indicated that the diseases differed based on the underlying genes. Dogs in the first group lost their vision when turned five years old.

By contrast, dogs in the second group showed more variation. Moreover, among the sick dogs, male dogs were overrepresented.

Apart from regular eye examinations, the research was also augmented by optical coherence tomography (OCT). OCT was never used before in veterinary medicine in Finland.

The imaging exposed the complete degradation of photoreceptors—cells that act in response to light stimuli—in dogs that suffered from type 1 atrophy.

Disease caused by a peculiar gene defect of the regulatory region

For the longest time, looking for the gene defect felt like looking for a needle in a haystack. We finally made a breakthrough after finding out that some of the healthy dogs have an almost identical locus of chromosome 15, only missing the mutation causing blindness. This implies that the mutation is a recent development.”

Maria Kaukonen, DVM, Study Principal Author and Postdoctoral Researcher, University of Helsinki

Prof. Lohi says, “The mutation we identified in the regulatory region results in hyperactivity in at least two retina genes previously associated with blindness. This is an interesting and uncommon find, as well as one of the first regulatory region mutations linked to retinal atrophy. Most likely, there are many more similar mutations, but they remain underrepresented in the literature due to the challenge of identifying them.”

Rectifying previous research findings

According to Prof. Lohi, “An American study published last year identified the same chromosomal locus as did our analysis, but the PPT1 gene in their proposal is actually associated with a very different disease of the nervous system, leaving us unconvinced.”

Prof. Lohi added, “Nevertheless, a commercial gene test was developed on the basis of these ambiguous findings, which has caused a great deal of confusion among dog owners and breeders. The gene variant identified by us has now been tested for in over 1,600 dogs, with the results matching the disease perfectly. Now, we will be able to design a reliable gene test for the breed to support breeding and diagnostics.”

The study forms part of Kaukonen’s recently approved doctoral thesis, which involved the investigation of the genetic causes of canine hereditary ocular diseases. It is also part of a greater research effort by Prof. Lohi’s team that analyzes the heredity of ocular diseases.

This study was the first to make use of the outcomes of the International DoGA Research project led by Prof. Lohi, the aim of which is to better understand the canine genome.

The DoGA project also employs scientists from the Karolinska Institute, Stockholm, Sweden.