Progressive Retinal Atrophy

 NORMAL VISION
Here is a very simple explanation of the process by which a dog „sees”:
Light passes through the lens and is directed onto the retina, which contains specialised photoreceptor (light-sensitive) cells called rods and cones. These cells convert the light into electrical nerve signals, which pass along the optic nerve to the brain, where they are „translated” into images.
  ~ rods are responsible for vision in dim light i.e. night vision
  ~ cones are responsible for vision in bright light i.e. daytime and colour vision
 DEFINITION OF PRA
  ~ Progressivea slowly developing disease process ~ the affected dog will gradually lose its sight and will usually adjust to its handicap
  ~ Retinalof the retina ~ the light-sensitive area at the back of the eye
  ~ Atrophydegeneration or deterioration ~ of the specialised light-sensitive cells in the retina
 DISEASE PROGRESSION
Initially, a dog with PRA will develop „night-blindness” i.e. it will eventually be unable to see in dim light conditions or in the dark. This is due to atrophy, or degeneration, of the rods. The owner may notice that the dog is reluctant to go out in the dark and hesitant to do down stairs in poor light. The dog may also appear to be a little „clumsy” i.e. bumping into things.
In the later stages of the disease, the cones are affected, and the dog’s daytime vision will gradually deteriorate.
PRA in Glens is thought to be „late onset” i.e. it is very unlikely that a Glen would show any degenerative changes (at eye examination) as a puppy. The range of ages, at which PRA has been first diagnosed in Glens, covers more than five years i.e. the youngest age, at confirmation of diagnosis, is 2 years and 2 months, and the oldest age, following previous „clear” eye examinations, is 7 years and 10 months.
 EYE TESTING
DNA tests for PRA have been developed for a number of breeds of dog. A blood sample is sent to a specialist laboratory for testing and the dog can then be classified as normal, a carrier, or affected. Please see LINKS for a list of the breeds for which blood testing is currently available.
Unfortunately, for the Glen of Imaal Terrier, and many other breeds, there is currently no test to determine genetic status for PRA i.e. we cannot do a simple blood test to identify whether a Glen is normal, a carrier or affected. For the time being, we have to rely on eye testing by a veterinary ophthalmologist. Eye testing can identify affected Glens. However, a „clear” test result cannot differentiate the normal Glen from the carrier Glen or even the Glen who goes on to test affected at a later date.
A „clear” test result simply means that the dog does not have any clinical signs of PRA on the day of the eye examination.
Eye examination should be carried out by a certified veterinary ophthalmologist. Your dog will be given some eye drops, to dilate the pupils. After about 20 minutes, your dog can be examined. The examination takes place in a darkened room; the vet will look into your dog’s eyes using an instrument called an indirect ophthalmoscope. This examination takes just a few minutes, and is a non-invasive and painless procedure for your dog!
You need to bring your dog’s registration documents with you when you have your dog’s eyes tested. The veterinary ophthalmologist will provide you with a certificate, valid for one year, detailing his/her findings. With effect from January 2010, all dogs in the UK must have some form of permanent identification (PI) e.g. microchip or tattoo, to be eligible to be certificated under the BVA/KC Eye Scheme. You will also need to bring along the PI documentation when yo have your dog’s eye tested.
Please see LINKS for a list of (UK) certified ophthalmologists.
Professor Peter Bedford is a certified ophthalmolgist in the UK. He is patron of the Glen of Imaal Terrier Association and attends one of their breed shows each year to conduct a subsidised eye testing session. Professor Bedford recommends that breeders have their litters routinely screened for congenital and hereditary eye anomalies. He suggests annual screening thereafeter.
 INHERITANCE
Inheritance of PRA in a couple of breeds of dog is known to be sex-linked, and it has a dominant form of inheritance in another couple of breeds. However, in the majority of breeds affected by PRA, the mode of inheritance is known or thought to be autosomal recessive.
The mode of inheritance of PRA in Glens is believed to be autosomal recessive, which means that the PRA gene has to be inherited from both parents for the dog to be affected. A dog with the PRA gene from only one parent will be a carrier; and a dog with no PRA genes will be normal.
  ~ Affected (pp)PRA gene from both parents
~ dog will eventually go blind
~ may test „clear” before being tested affected
~ if tested regularly, all affected dogs will eventually be identified
  ~ Carrier (Pp)PRA gene from only one parent
~ dog will have normal vision and will test „clear”
  ~ Normal (PP)No PRA genes
~ dog will have normal vision and will test „clear”
The dominant gene is denoted with a capital letter, in this case P. The recessive gene is then denoted with the same letter, but in lower case. The „dominant” letter goes before the „recessive” letter e.g. Pp represents a carrier i.e. the (dominant) normal gene (P) from one parent and the (recessive) affected gene (p) from the other parent.
Please see below for:
  ~ DiagramThis demonstrates how to work out the possible outcomes for a carrier x carrier mating.
  ~ TableThis shows all the combinations of outcomes for different matings.
  ~ Diagram demonstrating how to work out the possible outcomes for a carrier x carrier mating
The P gene from parent one and the P gene from parent twowill produce a PP (normal) Glen
The P gene from parent one and the p gene from parent twowill produce a Pp (carrier) Glen
The p gene from parent one and the P gene from parent twowill produce a Pp (carrier) Glen
The p gene from parent one and the p gene from parent twowill produce a pp (affected) Glen

Table showing all the combinations of outcomes for different matings
Parents Progeny (Offspring) Each puppy has a …
PP x PPNormal x Normalx= 100% chance of being normal
PP x PpNormal x Carrierx= 50% chance of being normal
50% chance of being a carrier
PP x ppNormal x Affectedx= 100% chance of being a carrier
Pp x PpCarrier x Carrierx= 25% chance of being normal
50% chance of being a carrier
25% chance of being affected
Pp x ppCarrier x Affectedx= 50% chance of being a carrier
50% chance of being affected
pp x ppAffected x Affectedx= 100% chance of being affected

For the time being, the only „certainties” regarding PRA in Glens are:
  ~ If a Glen is tested affected, its sight will deteriorate and it will eventually go blind.
  ~ If a Glen is tested affected, then both its parents – (if they are not known to be affected) – will be classified as „obligate” carriers.
  ~ If a Glen is tested affected, then all its progeny – (if they are not known to be affected) – will be classified as „obligate” carriers.
 BREEDING ISSUES
Breeds with a DNA test – (autosomal recessive mode of inheritance)
The advantage of having a DNA test for PRA is that breeders know the status of the dogs they are breeding, (if they are tested). This means that carriers, and even affecteds, can be selectively used in the breeding programme, without the risk of producing puppies that will eventually go blind as a result of PRA e.g.
SAFE matings, with known status dogs, are those that produce only normal or carrier puppies i.e.
  ~ normal x normal
  ~ normal x carrier
  ~ normal x affected
UNSAFE matings, with known status dogs, are those that can produce affected puppies, which will eventually go blind, i.e.
  ~ carrier x carrier
  ~ carrier x affected
  ~ affected x affected
Please see the table above for the combination of outcomes for different matings.
Breeds without a DNA test – (autosomal recessive mode of inheritance)
Breeding decisions are not easy with breeds that do not yet have a DNA test, particularly with „late onset” PRA (as in the Glen of Imaal Terrier), as there is no definitive means of establishing whether a dog is normal, a carrier or a „not-yet-known” affected.
Breeding considerations would need to include:
[i]   PRA status of parents and grandparents of the chosen dog and bitch and the wider pedigree e.g. siblings of parents/grandparents and their progeny (offspring).
[ii]  Age of first breeding.
[iii] Use of known carriers in a breeding programme.
Please go to PRA Pedigrees for a more detailed discussion about breeding issues relating to the Glen of Imaal Terrier.
 ACKNOWLEDGEMENTS
I should like to thank Maura High (Coleraine), Jean Rogers (Jeonty), Liz Gay (Malsville) and Professor Bedford for their help, advice and suggestions.