Progressive Retinal Atrophy (PRA)

Progressive retinal atrophy (PRA) is a group of eye diseases caused by progressive, degenerative or dysplastic changes in the retina.
The retina is the innermost layer of the fundus and contains the cells important for the visual process, the rods and cones. The rods (rod) are responsible for the light-dark vision, thus for the vision in the twilight and night and the cones (cone) for the day and thus color vision.
PRA occurs in almost every dog breed. However, different forms are distinguished. All hereditary forms are generalized and always lead to incurable blindness. Both eyes are always affected. Earlier developing, dysplastic forms of PRA appear in puppy age. Here, one or both photoreceptor types stop developing at a certain time after birth. The later developing forms manifest at different ages. The photoreceptors are initially fully differentiated in the late forms, but degenerate during the course of the disease and the retina and retinal vessels regress (atrophy).
The clinical presentation is similar in the late forms, but the age of manifestation and the course vary both between and within races. Also, different mutations may be responsible for the disease. It is possible that one mutation causes PRA in several breeds, but also that within one breed different mutations occur that lead to PRA. The first symptoms of the disease usually appear between the first and sixth year of life and depend on which type of photoreceptors degenerate first. Usually the rod cells of the retina are destroyed first, leading to increasing "night blindness". As the disease progresses, the other photoreceptor type is also destroyed and the dog goes completely blind. In addition, a lens opacity (cataract) may develop. Other signs of PRA are dilated pupils that react poorly or not at all to light and an increased reflective tapetum lucidum. Ophthalmologically, an atrophic retinal vascular network and pigmentary changes at the back of the eye are also noticeable.  With conventional examination methods, progressive retinal atrophy is usually diagnosed after the first breeding because the retinal changes are still minor at the onset of the disease. Electroretinography (ERG), which is often performed before cataract surgery, has the ability to measure the neuronal impulses emanating from the photoreceptors and thus diagnose retinal changes before the first appearance of clinical symptoms.  Studies have shown that PRA can be diagnosed approximately 2-5 years earlier with the use of ERG than without the use of ERG.

The rcd4 (rod cone dysplasia type 4) mutation refers to a late form of Progressive Retinal Atrophy that occurs in the Gorden Setter, Irish Setter, Polski Owczarek Nizinny and Tibetan Terrier. This form manifests itself at the earliest from the second year of life, often much later and is inherited autosomal recessively.
In the Tibetan Terrier, rcd4 together with PRA3 seems to account for only about 50% of PRA disease and other as yet unknown mutations seem to play a role. But in the Gorden Setter, Irish Setter and Polski Owczarek Nizinny breeds, the rcd4 mutation is thought to be responsible for a large proportion of late PRA disease. Therefore, a genetic test for the rcd4 mutation is available for these breeds.
More information about the genetic test and the submission form can be found here.

crd-PRA (cone-rod dystrophy) is an early form of progressive retinal atrophy in wirehaired dachshunds. Changes in the retina can be detected by fundoscopy from 10 months to 3 years of age. As early as 5-10 weeks of age, many puppies show enlarged pupils. By 5-6 years of age, retinal atrophy is complete in both eyes.
Loss of the retina results in loss of vision, leading to total blindness. In crd-PRA, the cones (cone) of the photoreceptor cells in the retina perish first, followed by the rods (rod). Therefore, in crd-PRA, there is first a loss of daytime vision and then night blindness.
By means of electroretinogram (ERG), damage to the cones can be detected at a very early stage.
A mutation (180 base pair deletion) in the NPHP4 gene (nephronophthisis 4) has been found in standard roughhair dachshunds with crd-PRA. This mutation in the NPHP4 gene has also been found in some lines of rabbit/dwarf greyhound dachshunds. In humans, mutations in this gene cause changes in the retina and additionally kidney disease, but this has not been detected in Roughhaired Dachshunds.
The crd-PRA mutation is inherited in a monogenic autosomal recessive manner.
More information about the genetic test and the submission form can be found here.