P.R.A.

Progressive Retinal Atrophy...

 

Written by:  PRA Task Force of the BMDCA

Edited by:
Dr. Gustavo Aguirre, VMD, Ph.D., Ph(hc)
Alfred H. Caspary Professor of Ophthalmology
James A. Baker Institute for Animal Health
College of Veterinary Medicine
Cornell University, Ithaca NY

Progressive retinal atrophy (PRA) is a hereditary disease of the eye that causes blindness.  The retina is the tissue lining the back wall of the inside of the eye and is composed of two classes of photoreceptor cells called rods and cones; the rods function in dim light, and the cones in bright light.  A PRA affected dog begins to have difficulty seeing in dim light, then gradually loses the ability to see in bright light, eventually becoming completely blind.  As the vision fails, the pupils become increasingly dilated, and may take on a shiny or iridescent quality.  When properly trained and managed most dogs can adjust to blindness well.

PRA is a blanket term for many types of retinal diseases, all of which result in blindness.  There are two groupings of PRA - early onset, and late onset.  In early onset PRA poor vision in low light may be detectable shortly after birth, with total blindness occurring from 1 to 5 years.  In late onset forms, night blindness occurs from 1 to 5 years, progressing to total blindness anytime after 3 years of age.  Early onset PRA has been diagnosed in Bernese Mountain Dogs (BMDs).   There may also be a late onset form of the  disease  in  the breed, but  this  has not  been definitively diagnosed.  There have been BMDs that have gone blind before the age of 2, and others who were diagnosed at age 9 who are not yet blind.

PRA is diagnosed by ophthalmoscopic examination by a Diplomate of the American College of Veterinary Ophthalmologists, or ACVO.  The pupils are dilated with eyedrops and the eyes examined.  The exam takes less than five minutes and the cost is variable, depending on whether the exam is performed at a public eye clinic or through private practice or a teaching hospital.  Approximate costs will usually range from $20 to $75.  Many dog clubs offer eye-screening clinics in association with dog events such as shows or matches.  Eye exams at these clinics, often referred to as CERF clinics, are generally the most affordable.  (The Canine Eye Registry Foundation is a non-profit closed registry that was founded to help combat hereditary eye diseases in dogs.) 

If an eye exam diagnoses retinal changes potentially associated with PRA, a more sensitive test may be needed in order to confirm that the dog has PRA.   The electroretinograph (ERG) measures the response of the rods and cones to specific colors of light.  Some ophthalmologists will do the ERG procedure without anesthetizing the dog, but the rigorous demands for accuracy in the research program we are following dictate that the ERG be performed while the dog is anesthetized.  When properly performed, an ERG provides the most definitive diagnosis, and is so sensitive that it can detect the presence of disease long before it can be seen by clinical examination.

PRA is hereditary and is always assumed to be an autosomal recessive trait until proven otherwise.  (A recessive trait requires two copies of the defective gene.  An autosomal recessive trait is one in which a recessive trait is carried on a chromosome pair other than the XY sex pair.) The Siberian Husky is the only breed as yet proven to have a different mode of inheritance, and it is sex-linked.   As a result, most of the PRA affected Siberian Huskies are male.  We have already been able to eliminate that possibility in BMDs.  An affected dog must have two copies of the defective gene.  A dog with only one copy of the gene is a carrier and will never have PRA, but will be able to pass that defective gene on to approximately half its offspring. 

At the present time, the only way to determine if a dog is a carrier is if one of its parents is affected, or if one of its offspring is affected.   Identifying carriers is imperative in order for breeders to make informed decisions and minimize the risk of producing PRA affected dogs.  To do this, all BMDs must have yearly eye exams, regardless of age or breeding status.  Results of these exams must be submitted to an open registry such as GDC (the Institute for Genetic Disease Control).   PRA affected dogs should be registered in the Berner-Garde database.  Silence in this case will increase the chances of producing dogs with PRA.

Dr. Gustavo Aguirre, the head of PRA research at the Baker Institute of Cornell University Veterinary School, and other genetic experts advise against using any affected dog, any known carrier, or any dog with a 25% or greater probability of being a carrier in any breeding program.  This is done in order to limit the spread of the defective gene, and to reduce the chance of inadvertently breeding a carrier to another carrier.   Offspring of an affected parent are always carriers or affected depending on the other parent.  Offspring of a known carrier have a 50% probability of being carriers if the other parent is genetically normal.  Grandchildren of a known carrier have a 25% probability of being carriers.  (These probabilities apply only over large numbers, and will not necessarily apply to a specific litter.)

The history of PRA:

• 1911 - PRA is first described in Gordon Setters.

• 1973 - First publicly reported case of an affected BMD in the USA, Hector v d Klosteralp.

• 1974 - Swiss PRA study includes an affected BMD, and provided evidence of autosomal recessive mode of transmission.

• 1978 - Second publicly reported BMD case in the USA, Roulette’s Ditto of Luci.

• 1995 - February Alpenhorn reported additional cases of PRA.

• 1997 - Three new PRA cases are made public establishing two high profile stud dogs as carriers of a gene for PRA.

• 1997 - PRA Task Force formed under the auspices of the BMDCA Health Committee.

The Baker Institute in Ithaca, NY, a research institute that is part of The College of Veterinary Medicine at Cornell University, is at the forefront of PRA research, and has begun studying PRA in the BMD.  The researchers there have developed a blood test for the Irish Setters that can positively identify carriers, affected and genetically normal dogs.  They have recently identified the gene locus and developed a blood test for another form of PRA that affects at least five dog breeds.   Blood samples submitted from affected BMDs have enabled the researchers to determine that the gene defect causing PRA in BMDs is not the same as the PRA gene defect in Irish Setters.  Just as finding the PRA gene locus which affects the Irish Setter breed presented a challenge to researchers, so does the search for the PRA gene in the BMD. 

It will take years, a great deal of money, and the dedication of BMD owners to do the genetic research necessary to develop a test for the defective gene(s) in BMDs.  It is essential for all affected dogs to participate in the research project by submitting blood samples and pedigrees.  The identification of affected dogs should be  communicated to Task Force co-chairs Fran Krauss and Ellen Jacobs who will provide contact information to the Baker Institute.  They can be reached at (650) 355-3355.  All information submitted will remain strictly confidential.

We need to be aware that this research is time consuming, effort intensive, and EXPENSIVE.  Fund raising by BMD clubs and their members will help speed the progress of the research.  Identification of the PRA gene in BMDs will ultimately enable us to eradicate this disabling genetic disease.

PRA Task Force:  Fran Krauss, Ellen Jacobs, Lori Jodar, Valerie Horney, Mary-Ann Sontag, Pat Long, Dr. Kathy Berge, DVM advisor.

For Baker Institute liaison or other PRA Task Force information:  Fran Krauss and Ellen Jacobs at (650) 355-3355,                           < berners@dnai.com >

For information about Berner-Garde:  call (500) 447-0090.

For information about GDC call (530) 756-6773.

For additional pamphlet copies:  Pat Long,                                       < berner1@concentric.net >