Hemeralopia

Information about Day Blindness in Standard Poodles
By Dr. Kristina Narfstrom

We are currently involved in a study of day blindness in a litter of standard poodles. According to the breeder, this problem has been observed previously in the breed in the USA. Due to our long standing work with hereditary retinal diseases in dogs we became involved in a study to characterize this disease clinically and electrophysiologically and to find the genetic defect for the disorder. Therefore, affected and non-affected dogs were studied using regular ophthalmic examination methods and electroretinography (ERG). The latter is an objective test for retinal function. Also, blood from affected dogs and their close relatives (littermates and parents) was sent for future molecular genetic studies at the University of Missouri.

So far we have been able to study clinically a total of 5 related dogs, between ages 4 to 12 months. Two of these dogs have been affected by day blindness since age 5-6 weeks (observation by the breeder). Initial findings were that the two littermates “were running into things” in bright daylight. Indoors, as young puppies, they behaved quite normally, and especially in low lighting conditions. The external appearances of their eyes were normal.

 Clinical examinations showed that they had abnormally slow pupillary light reflexes and, when looking into their eyes with specific equipment, the back of the eye (the fundus) looked abnormal in 2 of the dogs (change in color of the fundus and in structure of the retinal vasculature). ERGs showed severely reduced visual function in low lighting conditions, while their visual function in bright light was non-recordable. We have been able to examine the 2 affected dogs twice, 6 months apart, and there is a slow, progressive deterioration of their visual function with time. The end stage is therefore, most likely, complete blindness. The visual handicap of the affected dogs does not appear to affect them mentally in any significant way. They are wonderful dogs, able to move around quite happily in, for them, well-known surroundings. This will probably still be the case when the disease has progressed even to its end stage.

 At the University of Missouri we are very interested in helping out with further characterization of this disease and with finding the gene defect for this retinal disorder that appears to be hereditary in the standard poodle breed. For this we would like to know about any other affected dogs you find in the standard poodle population.

 Professor Kristina Narfstrom , DVM, PhD, DiplECVO
Phone (direct): 573 882 2095 narfstromk@missouri.edu 

Professor Gary Johnson, DVM, PhD
Phone (direct): 573 882 6723 johnsongs@missouri.edu 

For further information about shipping and handling blood samples from affected dogs, and their close relatives, see: www.caninegeneticdiseases.net

---

Author: Heather Bryan

In the past twenty years, I have seen science give the dog world seemingly marvelous tools to aid in the diagnosis and prevention of some serious genetic health issues. The ongoing research into the DNA of many breeds for specific known health issues offers great promises towards the future of overall dog health. Many of these research projects started as a collaboration of breeders who have had serious health issues crop up within their lines, veterinarians who diagnosed such issues, and universities who were willing to delve deeper into the problem.

Addison’s, epilepsy, sebaceous adenitis, toe cancer, and Chrondro Dysplasia are a few of the more publicized issues being worked on by various universities. However, with all the innovations we have at our beck and call, it seems that more and more health issues are surfacing . . . some of which have been lying below the surface for an unknown period of time.

It was mid July when I first noticed symptoms in one of our puppies. The litter was born at the end of May and, when they were about six weeks old, one of the females began showing signs of weak vision in the sunlight. I observed her for a few days, saying nothing until I was certain there was a problem. It seemed to only affect the puppy when she was outside in bright light: when the puppies were inside, her vision seemed normal. By the time the puppies were seven weeks old, a second puppy – also female – began showing signs of the same vision problem. This litter was a line breeding, doubling up on an outside line not related to our own.

I immediately contacted the breeder of the sire of this litter and explained the symptoms to her as I had observed them. She confirmed she had also had several litters that had puppies with similar symptoms; that several of these puppies had been euthanized and necropsies performed on them. She agreed to have the necropsy reports forwarded to me via a mutual friend. Next, I turned to the Internet to see if I could find more information as well as a scientific diagnosis. My Google search for “day blindness in dogs” turned up a word I could barely pronounce, but that I soon became very familiar with over the ensuing months: Hemeralopia.

So, what, you may ask, is Hemeralopia? I read an article by Dr. Kenneth Bourns titled Day Blindness, which documented a line of Alaskan Malamutes, who, back in the 1960s, produced puppies who seemed to have problems seeing properly during the daylight. It chronicled how the breeder was able to work with scientists through controlled breeding to help eliminate this disease from the line without destroying the existing breeding program.

After reading the article, I knew I needed to track down the origin of the problem in the puppies. Over the course of the next few weeks, I contacted universities and ophthalmology research facilities, mostly, with little result. Most were not interested in opening research into what outwardly appeared to be an isolated case. It was by shear chance I received an email at the beginning of August from the University of Missouri, Columbia reporting the results from blood-work I had submitted in early June. The dog tested had been clear of the disease (which was wonderful news) but, more than that, the timing of the results could not have been more perfect. I quickly replied to the email giving a brief synopsis of the symptoms seen in my puppies, and it was forwarded to Dr. Gary Johnson, head of the genetics research lab. The University of Missouri, Columbia has done extensive research on NE (Neonatal Encephalopathy with Seizures) and recently provided a DNA test to screen Standard Poodles for the disease.

Within hours of my initial request, I received a response from Dr. Johnson. He was both helpful and resourceful, and immediately offered his assistance in exploring this disease in Standard Poodles. At the time of our initial contact, there was a veterinary conference overseas and his staff was short handed; however, he mentioned the potential interest to Dr. Kristina Narfstrom, who is well-known for her research on diseases of the eye. Within a few weeks, we had most of the litter CERF’d (the eye health results were completely normal). At the request of Dr. Johnson, we then had blood drawn from both the litter and the mother, and these samples were sent to UOM (University of Missouri).

With the aid of UOM, we coordinated with a local office of the Eye Clinic for Animals to have an Electroretinagram (ERG) performed on the affected puppies. Dr. Narfstrom flew to Phoenix for the procedure. Two of the affected puppies were tested, as well as two unaffected puppies from different litters. The initial results were quite clear. The affected puppies did indeed have day blindness, and it was indeed genetic.

The gene that produces day blindness is recessive, which means that both parents must be carriers for it to be produced. With both parents as carriers, typically 25 percent of the litter will be born affected, 25 percent will be carriers, and the remaining 50 percent will be unaffected. There were eight puppies in this litter. With two affected, it fell in line with the statistics. Because it takes two carriers to produce this disease and because there is currently no way to screen for it, it can go silently through a breeding program and be passed on from generation to generation without any puppies being affected.

From the time I realized we had a litter of affected puppies, I made it perfectly clear that my intention was to help rid the breed of this disease. As soon as we recognized we had a genetic issue on our hands, we neutered both parents of the litter so there was no chance that either could ever pass this disease on in the future. Unfortunately, there has been some dissension from other breeders who would have preferred to have this matter kept from the public – a “code of silence” as it were. After publicizing our problem, we have been contacted by numerous breeders and owners who have known or witnessed affected puppies with similar symptoms.

---

Author: Heather Bryan

As many of you know, in the summer of 2007, we had a litter of Standard Poodles of which two females, about six weeks of age, began showing signs of vision difficulty in bright light. Our initial diagnosis was confirmed in October when Dr. Kristina Narfstrom of the University of Missouri Columbia flew to Phoenix to perform ERG’s (Electroretinagram) on the affected puppies, as well as two unaffected Poodles, which allowed her to confirm the diagnosis. Nearly six months later, Dr. Narfstrom returned to Phoenix to perform follow-up ERG‘s and document any changes. Unfortunately, there was noted deterioration in the vision of both affected puppies.

Both affected puppies have remained here in the Phoenix area and have wonderful homes! They are doing so well that, although they are now nearly blind, they don‘t let that stop them! They both live with great families who adore them. Hopefully, sometime in 2009, Dr Narfstrom will return to Phoenix for another follow-up ERG.

This past summer, I was contacted by a breeder who had a litter of Standard Poodles that had several puppies who showed signs of being day blind. At the time, she had no idea of the cause and was advised to euthanize the affected puppies, which she did. It was only after she read the articles posted about Day Blindness in Standard Poodles that she realized there was likely a connection. Notably, she indicated that the pedigree of her litter had quite a few common ancestors whom we now believe to be the strong link as a probable source of the disease.

This past February, I was contacted by a couple who had purchased a Standard Poodle puppy six weeks earlier. They had noticed he had odd behavior when he was outside in bright sunlight. After consulting their veterinarian and doing hours of research online, the woman came across an article I had written about my experiences with day blindness in Standard Poodles. The symptoms described were eerily similar to her dog’s, so she contacted me for any information that I might be able to provide. Immediately, I gave her Dr Narfstrom’s contact information, and advised her to contact an eye specialist so that they could get a medical diagnosis of her puppy.

Since the initial contact was made with me, the puppy has been returned to the breeder. On April 10th, 2009, Dr. Narfstrom flew out to the office of the breeder’s veterinarian and performed ERG’s on the three remaining puppies in the litter. Of the puppies tested, two were confirmed to have inherited Hemeralopia from their parents.

There was a notable vision difference between the two puppies in this litter and my own litter. My girls showed more advanced vision loss at the time of their initial ERG, while the puppies from this litter had more visual capabilities. I wrote to Dr. Narfstrom about this, and here is a bit of her response to the issue:

“As I explained earlier I found that two of the three puppies that were examined with ERGs were affected by cone rod dystrophy causing mainly day blindness at this point in time. It appears that it is the same kind of disease I see in these puppies as the disease we saw in Heather's dogs. The main difference is that the disease in Heather's dogs was more advanced, even at the first time of examination (done when the dogs were four-six months old).

“This is not an uncommon finding when it comes to cone rod problems. In the Dachshund, for example, with the cord1 mutation, there is a great heterogeneity that has been described for the disease. This means that some dogs get it very early on and go blind early while some get it later in life and don't seem to lose vision completely. But all of this needs to be studied in the Standard Poodle more thoroughly, and I hope to go back to do follow-up ERGs in about four months.

“I suspect that the gene defect (the mutation) is the same in both (litters). Therefore we should continue to work with finding more affected dogs so that blood can be collected, as well as pedigrees, in order to find the specific mutation and provide a test for this disorder.”

On a side note, I should let you know that this current litter of puppies was raised in a state that has severe winters, and that the litter spent no time outside prior to going to new homes in January. I feel as though this may have played a part -- or at least have been a contributing factor – in the degree of actual vision loss to date. The girls from my litter, on the other hand, have spent their lives in very sunny Arizona.
The breeder of the litter with the Day Blind puppies wrote this note to me after I had completed the article: Last night, when I finally had some time to think about the above statement in your article,
it isn't necessarily true. Gustafe spent approximately 2 months in sunny Florida where he was outside most of the daylight hours according to the schedule his owners sent home with him. His testing showed much better reception than the little girl who spent her time indoors. Gustafes' rods were normal, the cones were bad.
Pedigrees of the grandparents to the new Day Blind puppies;
Dam: DHP's Mocha Latte Sweetheart # PP66459902
Sire: Hooligan, My Heart's Desire #PP63087001

Dam: Kit-Sue's Skylar HighDollar #PP660784/01
Sire: Smith's Tuxedo Jacque #PR032756/03
Not long after I was contacted by the puppy owner with the affected puppy, I spoke with Dr. Narfstrom about the on-going research. One of the most fascinating things I left the conversation with is that, with the technology the University of Missouri Columbia has available today, they will probably be able to find the DNA marker for this disease with blood work from as few as six to ten confirmed affected Standard Poodles. They now have blood work from four affected dogs, as well as at least a dozen closely related Poodles. They could possibly have a DNA marker within the next two years.

The Genetics Research lab at the University of Missouri Columbia is always in need of blood samples from dogs who may have a strong relation to the known affected Poodles. To view the pedigree’s of the parents of my litter, I’ve posted the following links.

http://www.poodlepedigree.com/pedigree.asp?ID=332323 
http://www.poodlepedigree.com/pedigree.asp?ID=333864 

If you have a Standard Poodle who has common ancestors in the above pedigrees, we strongly encourage you to donate blood samples to the University of Missouri’s Genetics Research Lab. The following link is the form that should be filled out when submitting the blood samples.

Note: There is no fee involved in donating blood as this is a research project. When filling out the form CROSS OUT “Test Being Requested” and write “Requested blood sample for Standard Poodle Dayblind Research.”

http://www.caninegeneticdiseases.net/DNAtests/TESTSnow.htm 

You can also contact the office directly for more information. Liz Hansen is extremely helpful with information. Her email address is:

hansenl@missouri.edu  and the office phone # is (573) 884-3712

The International Parti Poodle Club is also working on ongoing fundraising for the University of Missouri Columbia’s research of this disease. For more information please visit:

http://dayblind.org/