Progressive Retinal Atrophy

Progressive Retinal Atrophies or PRAs are a group of degenerative diseases affecting the retina of the eye. In the retina are cells specialized in detecting light: those are photoreceptor cells. In dogs affected by PRAs, these cells degenerate over time (atrophy), which leads to blindness. This syndrome is unrelated to Collie Eye Anomaly (CEA).

Collies (rough and smooth) have a unique type of PRA not found in other breeds, called rod-cone dysplasia 2 or rcd2. PRA-rcd2 is a very early onset retinal atrophy, as by 6 weeks of age affected puppies can already present with night-blindness. By 6-8 months, most affected puppies are completely blind.

Thinning of the retina due to PRA-rcd2 can be detected by a Board Certified Veterinary Ophthalmologist. The eyes are dilated prior to the examination, so the interior of the eye can be examined with an ophthalmoscope. Lesions are generally symmetrical, with both eyes affected identically, unlike CEA where lesions are generally different between both eyes.

First identified as a disorder in the 1970s, it was quickly identified that PRA-rcd2 is an autosomal recessive disorder, which means two copies of a defective gene are needed to show symptoms. It took until 2006 to identify the mutation, and a test was later developed by to identify it easily.

Collie Health Foundation has been proudly funding research on PRA-rcd2 since 1991 and has negotiated a discount on PRA-rcd2 tests for its members through Wisdom Health. More information here!

PRA-rcd2 Genetic Results and Their Meaning

Mutant/Mutant: Affected – These dogs carry two copies of the mutation and will be affected by PRA-rcd2.

Mutant/Normal: Carrier – These dogs carry one copy of the mutation and will not be affected by PRA-rdc2. They may produce affected dogs, depending on the dog they are bred to.

Normal/Normal: Normal – These dogs do not carry any copies of the mutation and will not be affected by PRA-rcd2. Their offspring will not be affected by PRA-rcd2, but may be carriers, depending on the dog they are bred to.

History of PRA-rcd2: Test Breedings

In the absence of a genetic test, breeders had to resort to test breedings to identify carriers in their breeding program. This was a heart-wrenching process: the dog of unknown PRA status would be bred to a blind (affected) dog. If even one offspring was affected by PRA-rcd2, the dog would be confirmed as a carrier. All offspring from these test breedings would be either affected or carriers, depending on the PRA status of the unknown dog. This can be represented using Punnett Squares:

Punnett squares of crossed between a carrier or normal dog and an affected dog.

These two Punnett squares show the result of a cross between and affected (blind) dog and either a carrier or a normal dog. Only the cross with a carrier can produce blind puppies.

The Science

The mutation responsible for PRA-rcd2 was identified in 2006 by Kukekova and coworkers through a genome wide scan, similar to the one currently ongoing to identify the mutation(s) responsible for higher grades of CEA such as colobomas. The mutation was mapped to the gene RD3, which is known to be essential in the development of light-sensing cells in mammalians. In humans, mutations of RD3 are associated with retinal dysplasia such as Leber congenital amaurosis. In the PRA-rcd2 affected dogs, 22 extra base pairs are added to the gene sequence of RD3, which changes the last 61 amino acids of the encoded protein. The true function of the RD3 protein, however, remains unknown

References

Wolf, E. D., Vainisi, S. J., Santos-Anderson, R. (1978). Rod-cone dysplasia in the collie. Journal of the American Veterinary Medical Association, 173 (10), 1331-1333. https://europepmc.org/article/med/730609

Kukekova, A. V., Nelson, J., Kuchtey, R. W., Lowe, J. K., Johnson, J. L., Ostrander, E. A., Acland, G. M. (2006). Linkage mapping of canine rod cone dysplasia type 2 (rcd2) to CFA7, the canine orthologue of human 1q32. Investigative Ophthalmology & Visual Science, 47 (3), 1210-1215. https://doi.org/10.1167/iovs.05-0861

Kukekova, A. V., Goldstein, O., Johnson, J. L., Richardson, M. A., Pearce-Kelling, S. E., Swaroop, A., Friedman, J. S., Aguirre, G. D., Acland, G. M. (2009). Canine RD3 mutation establishes rod-cone dysplasia type 2 (rcd2) as ortholog of human and murine rd3. Mammalian Genome, 20(2), 109–123. https://doi.org/10.1007/s00335-008-9163-4

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