Researchers Seek Genetics Behind Poodle Eye Diseases


Diligent breeders regularly health test their breeding stock before including them in planned litters. Eye examinations, one of the required tests for all varieties of Poodle to obtain Canine Health Information Center (CHIC) certification, are important to identify vision disorders such as optic nerve hypoplasia (ONH), micropapilla (Mp) and juvenile cataracts.

CHIC certification also requires Miniature and Toy Poodles to be DNA-tested for the progressive rod-cone degeneration form of progressive retinal atrophy (prcd-PRA). The late-onset disorder causes night blindness and eventually total blindness due to the degeneration of cells in the retina in the back of the eye that appear normal early in life.

Miniature Poodle breeder Sally Ciraolo of El Cajon, California, is a diligent breeder. Before breeding her 5-year-old brown bitch “Asa” (CH Pearl’s Indulgence To Mivida), she had the dog’s eyes examined by a veterinary ophthalmologist, who determined they were clear of eye disease. Although the sire’s eyes had not been health tested, his sire and dam also had tested clear.

When the puppies were around 8 weeks old, Ciraolo grew concerned that one female puppy looked to the ceiling when she entered the room and spoke to them. “I suspected a vision problem, so I took the whole litter and Asa to the veterinary ophthalmologist,” she says. “The veterinarian determined that this puppy was blind due to optic nerve hypoplasia. Later, I learned that Asa has Mp in one eye despite having had four previous clear eye examinations.”

Optic nerve hypoplasia is a rare genetic defect, affecting one or both eyes, in which the optic nerve fails to develop normally. Although it is believed that the condition has an autosomal recessive inheritance, it is possible that one gene controls the disease predisposition and additional modifying gene(s) influence the expression and severity of the disorder. Micropapilla describes a condition in which dogs have abnormally small optic discs, though it usually is not associated with a visual deficit. It is not known whether Mp is part of the ONH disease continuum or a separate condition.

The Poodle Club of America (PCA) Foundation wants to advance understanding about the genetics behind ONH and Mp as well as juvenile cataracts. The Foundation has funded a three-year study led by Gus Aquirre, VMD, PhD, DACVO, professor of medical genetics and ophthalmology at the University of Pennsylvania, in conjunction with OptiGen, a genetic testing laboratory for canine health conditions. Dr. Aguirre, the geneticist who discovered the mutation for prcd-PRA in Toy and Miniature Poodles in 1998, is optimistic about the possibility of identifying the causative genes for these disorders, providing enough DNA samples are submitted to support the research.

Understanding Similar Eye Disorders 
Although ONH is a rare condition, more Miniature Poodles are affected than any other breed, says Dr. Aguirre. “A congenital disorder, ONH varies in severity based on how much it diminishes the optic nerve,” he says. “Visual deficits range from hardly noticeable to complete blindness.”

The optic nerve, located within the optic disc at the back of the eye, is made up of nerve fibers that connect retinal cells with visual centers in the brain. The optic disc appears grayer and abnormally small in dogs with ONH due to fewer nerve fibers. This means that the brain receives fewer signals for light reception.

One aim of the genetics study underway at the University of Pennsylvania is to determine whether Mp is associated with or independent of ONH. “We believe that Mp represents a midway point between normal and ONH,” says Dr. Aguirre. “Besides the smaller optic disc, the pupillary light reflexes, which cause the pupils to constrict in response to light, are normal in dogs with Mp, but abnormal in those with ONH. If vision impairment is mild in dogs with ONH, it is hard to tell the difference between ONH and Mp.”

Mp occurs sporadically and ONH occurs even more infrequently, though in Miniature and Toy Poodles ONH is more prevalent. Besides Poodles, breeds affected by ONH include: Beagle, Border Collie, Bullmastiff, Collie, Dachshund, English Cocker Spaniel, German Shepherd Dog, Great Pyrenees, Irish Wolfhound, Miniature Pinscher, Miniature Schnauzer, Norwich Terrier, Nova Scotia Duck Tolling Retriever, Saint Bernard, and Shih Tzu.

Diagnosis of both conditions requires an ophthalmoscopy examination in which a board-certified veterinary ophthal­mol­­ogist evaluates the retina, retinal blood vessels and optic nerve disc. Puppies can be examined as early as 8 weeks of age, even before going to new homes.

Doreen Becker, DVM, PhD, is working with Dr. Aguirre at the University of Pennsylvania to build the family pedigree information of dogs affected by ONH and Mp. “Thus far, we have found a common founder that connects all dogs affected with ONH,” she says. “This suggests a recessive transmission for both disorders, with micropapilla having a milder infestation. Thus, it is likely that ONH is caused by one gene with additional modifying genes influencing its severity. However, the true inheritance pattern will not be clear until we identify a gene. Right now, we are hypothesizing there is a recessive mode of inheritance.

“If we receive more samples, we will be able to make a more reliable assumption about the inheritance pattern and the connection between ONH and micro­papilla. Information about related animals and their vision status will help us determine the transmission when we identify possible causative gene(s).”

Dr. Aguirre advises Toy and Miniature Poodle breeders not to breed dogs that have not been tested for these eye conditions. “Furthermore, until we know the gene mutation, affected dogs should not be bred,” he says. “Breeders should continue to have eye examinations of their litters when they are from 8 to 12 weeks old, as these conditions can be identified in puppies.”

The Genetics of Cataracts
Similar to the ONH and Mp research, the juvenile cataract study funded by the PCA Foundation focuses on identifying the genetics behind the early-onset disease. With an incidence rate of 6 percent, Miniature and Toy Poodles have one of the highest juvenile cataract rates of all breeds. An autosomal recessive inheritance pattern is suspected though it has not yet been proved.

Cataracts are a leading cause of blindness in dogs and humans. They occur when the clear lens of the eye, used for focusing light in the retina at the back of the eye, develops cloudy spots that gradually inhibit light from reaching the retina. As the lens gets cloudier, it dims the light reaching the retina until the dog may become completely blind. Although not painful, cataracts increase the risk of an injury particularly when a blind dog is in an unfamiliar environment.

Hereditary cataracts occur in at least 70 breeds. Despite the large number of breeds affected, little is known about the genetics of the condition. Cataracts have breed-specific characteristics that relate to appearance, age of onset, rate of progression, and whether they occur in both eyes.

In Toy and Miniature Poodles, dogs are born with normal lenses that gradually lose their transparency around 2 to 5 years of age. Cataracts in Poodles can involve the nucleus, or central part, of the lens, as well as the lens cortex, or more peripheral layers. The rate and degree of progression varies.

Although the cataract research is in the early stages, the University of Pennsylvania researchers consider the work promising. “We have already excluded 
a number of genes,” Dr. Aguirre says.

Discovering a dog has a blinding eye disease can be devastating. Taking part in studies, such as these funded by the PCA Foundation, offers hope that the causative gene mutation(s) will be found. A DNA test for these conditions may one day allow breeders to breed away from the disorders and produce normal sighted dogs.

The importance of submitting blood samples and health information about dogs affected by eye diseases cannot be understated. Without contributions, the research may not progress. Ciralolo, the Miniature Poodle breeder whose bitch Asa produced an ONH-affected puppy, promptly mailed test findings and DNA samples from the litter to the researchers.

“I am looking forward to when we will have a DNA test to help us breed healthy dogs without the risk of these eye diseases,” Ciralolo says. “It is exciting to be part of helping to advance the visual health of our breed.”

Purina thanks Leslie Newing, editor of The Poodle Papers, for helping us to identify this topic for the Poodle Update.

CHIC Eye Testing for Poodles 
Due to the prevalence of eye diseases in Poodles, all varieties are required to have eye tests to receive health certification through the Canine Health Information Center (CHIC). Eye examinations should be performed by a veterinary ophthalmologist certified by the American College of Veterinary Ophthalmology and results should be registered with the Orthopedic Foundation for Animals (OFA) or Canine Eye Registry Foundation (CERF). Test results from OFA and CERF databases are shared with CHIC at no cost to owners. In addition, Toy and Miniature Poodles should be DNA-tested for the progressive rod-cone degeneration form of progressive retinal atrophy. For more information, visit the variety-specific requirements on the CHIC website.

Contributing to PCA Foundation Vision Studies
Owners of Miniature and Toy Poodles diagnosed with optic nerve hypoplasia, micropapilla or juvenile cataracts may contribute to genetics research funded by the Poodle Club of America (PCA) Foundation. The three-year study, which began in 2014, is underway at the University of Pennsylvania in conjunction with OptiGen, a genetics testing laboratory for canine health diseases.

The studies focus on these Poodle varieties, as the conditions occur more commonly in them, though owners of Standard Poodles diagnosed with these conditions may submit samples as well. For information about participating and to download the submission form, please visit the OptiGen website.