Breeders Welcome New DNA Test for Primary Lens Luxation

Terrier breeders who have had dogs that suffer from primary lens luxation (PLL), a painful, genetic eye disorder that often leads to blindness, shared relief when the gene mutation was discovered last fall by researchers at the University of Missouri, and the Animal Health Trust and the University of Cambridge, both in the United Kingdom. By mid-September a DNA test was available for PLL, allowing breeders to test dogs to determine which ones are carriers, affected and normal. In some breeds, as many as 50 percent of dogs are believed to be carriers, says Cathryn Mellersh, Ph.D., a researcher at the Animal Health Trust.

Primary lens luxation has been reported in more than 45 breeds of dog and is most common in terriers. Parson Russell Terriers, Jack Russell Terriers, Miniature Bull Terriers, Bull Terriers, Patterdale Terriers, Sealyham Terriers, Fox Terriers, Toy Fox Terriers, and Rat Terriers are among the affected terrier breeds. A late-onset disease, PLL typically does not appear until dogs are between 4 and 8 years of age — long after many have been bred. About 10 percent of cases occur in dogs older than 8 years old.

Emergency treatment is necessary, for lens luxation, yet signs of the disorder are subtle and many owners fail to recognize them. By the time a dog is squinting and the eye is swollen or red, he is likely in considerable pain. If pressure in the eye goes without treatment for more than 72 hours or if bleeding occurs in the eye, the chance of saving a dog's vision is low.

On one Web site describing PLL, an owner reported going to bed at night and her dog being fine. In the morning, the dog shuddered in pain when the owner tried to look at his eye, which was cloudy. Though the dog was rushed to the veterinarian, it was already too late to save the eye.

In another example, an owner returned home after a few hours away to find her dog with both eyes shut, in pain and immobile. The emergency veterinarian prescribed eye drops to reduce the pressure within the eye, but by the time a specialist examined the dog two days later, the pressure was unchanged and the eye had to be removed.

In a sense both cases had happy endings. The partially luxated lenses in the dogs' eyes were detected in time so that, with medication for one dog and surgery for the other, their vision in the remaining eyes was saved. Signs of lens luxation aren't always so dramatic. Fortunately, the new DNA test allows owners of susceptible dogs to be forewarned.

When Lens Luxation Occurs The canine eye is similar to the human eye. Light goes through the outer clear cornea, passing through the watery aqueous chamber, and enters the pupil, the round opening in the middle of the colored iris. Light traverses through the lens, then the vitreous chamber and finally is absorbed by retinal receptors.

The lens is held in place by a network of tiny fibers, called zonules, that attach the lens perimeter to the ciliary muscle that rings the eye similar to a round trampoline, with the zonules serving as springs that attach the trampoline (lens) to the frame (ciliary muscle). If these springs were to break, the trampoline would fall from the frame.

In some dogs, the springs do break — or described more accurately, the zonules pull away from where they're attached to the lens. If only some of the zonules become detached, one edge of the lens floats around, but the lens is basically held in place. This condition is called subluxation. Signs of subluxation include a crescent shape (actually the side of the lens) visible through the pupil and a trembling iris, especially when the eye is moved. The eye may also be slightly reddened.

Administering eye drops to constrict the pupil can sometimes help prevent a subluxated lens from getting worse, and especially from falling forward through the pupil. Even so, the increased tension placed on the remaining zonules, coupled with their genetic weakness, usually results in increasing breakages and more extensive detachment to the point the lens becomes fully detached, or luxated.

A luxated lens can fall either toward the front or the rear of the eye. Most often, it drifts forward (an anterior luxation), where it may rub on the iris, poke through the pupil opening, and even abrade the inner surface of the cornea. This can cause pain as well as corneal swelling and clouding if not corrected quickly. Worse, it can block the flow of aqueous fluid through the pupil and through the drainage angle, or the part of the eye at the juncture of the cornea and iris edge that is responsible for aqueous fluid to flow out of the eye. A lens that drifts backward (posteriorly luxated) can also block the drainage angle because of the vitreous that may be displaced forward.

The trapped aqueous builds up like water in a balloon, causing increased intraocular pressure and glaucoma. This increased pressure is not only painful, but also potentially blinding — and quickly. If the pressure isn't alleviated within 72 hours (sometimes sooner), it will usually cause irreversible damage to the retina and optic nerve, resulting in cell death and permanent blindness.

If less than 72 hours has passed and the intraocular pressure isn't severe and the retina and optic nerve still look healthy, there's a fairly good chance of retaining vision by surgically removing the entire lens. Removing the lens leaves the eye severely farsighted, but it is possible, although challenging, to replace it with an artificial lens that will restore fairly normal focus. Lens replacement is more difficult in these dogs compared to dogs with cataract surgery because in the latter the entire lens isn't removed.

Although some cases of lens luxation are caused by trauma, severe cataracts or other conditions, most cases are hereditary. When lens luxation is not secondary to another cause, it's known as PLL. In hereditary cases, once the lens in one eye has luxated, the lens of the other eye usually luxates within months. An ophthalmologist may catch early signs, such as a wobble to the lens as the eye moves, indicating that the zonular ligaments are loosening. When this occurs, it's usually best to remove the loose lens before it luxates, thus averting a crisis that requires emergency surgery.

PLL has a recessive mode of inheritance. Because of the late age of onset, as well as the fact that carriers usually exhibit no signs, breeders have long wished for a way to identify the gene or genes that cause the disease. Working independently and studying different breeds, teams of researchers in the United States and the United Kingdom found the mutation responsible for PLL.

Gary Johnson, D.V.M., Ph.D., and Elizabeth Giuliano, D.V.M., M.S., DACVO, of the University of Missouri College of Veterinary Medicine, led the effort in North America. Mellersh of the Animal Health Trust and David Sargan, Ph.D., of the University of Cambridge Department of Veterinary Medicine, studied the disease in the United Kingdom. The mutated gene causes changes even before luxation has occurred. "The fibrils (zonules) that hold the lens in its place attached to the ciliary body become detached at the lens end and appear disordered even in quite young dogs homozygous for the mutation," Sargan explains.

Reducing PLL with Genetic Testing Now owners of certain breeds — Australian Cattle Dog, Chinese Crested, Jack Russell Terrier, Lancashire Heeler, Miniature Bull Terrier, Parson Russell Terrier, Rat Terrier, Sealyham Terrier, Tibetan Terrier, and Welsh Terrier — can order a DNA test kit through the Orthopedic Foundation for Animals Web site at www.offa.org. A cheek swab is used to collect the sample, which is sent for testing to the Animal Molecular Genetics Laboratory at the University of Missouri.

Analysis of the sample will show if a dog has:

  • Two normal copies of the gene (Normal);
  • One normal copy and one mutated copy (Carrier/Low Risk); or
  • Two mutated copies (Affected/High Risk).

Owners in the United Kingdom can test their dogs through the Animal Health Trust. For information, go to www.aht.org.uk.

Genetically affected dogs with two copies of the mutant gene are at high risk of developing PLL at some time in their life. Normal dogs with two copies of the normal gene are at negligible risk. Carriers with one normal and one mutant gene have a slight risk of developing PLL. Researchers don't know why some carriers develop PLL but suspect it may be a combination of genetic and environmental factors. When carriers develop PLL, they tend to do so at a slightly older age than do genetically affected dogs.

In the past, breeders were advised to remove affected and carrier dogs from the breeding population. In practice, this wasn't always possible. Not only were many affected dogs bred before their condition became known, but in some breeds, the condition is so widespread that breeders had to breed possible carrier to possible carrier and take their chances.

The DNA test changes that. "We'll no longer have to worry about breeding this hereditary disease and worrying if we've produced affected puppies," says Deb Guerrero, health coordinator for the Miniature Bull Terrier Club of America. "Before the DNA test, all we could do was look at pedigrees that we knew had many carriers and affected dogs, mark the pedigrees as such, and try to make the best choice when we did a breeding."

With the DNA test, dogs can be bred to avoid producing PLL. Even affected dogs and carriers can be bred, as long as they are bred to normal dogs. It's true that the carriers they produce will have a slightly higher than normal rate of PLL, but in some breeds, that's the lesser of possible evils.

"Our preliminary work indicates that in some breeds close to 50 percent of dogs are carriers," Mellersh says. "This means that breeders should continue to breed with their carriers for a few generations at least to avoid severely reducing genetic diversity. With sensible use of the test and patience, owners and breeders can look forward to a future without PLL."

Whereas before DNA testing, the goal was to remove carriers from the breeding population, newer breeding strategies recognize that dogs cannot be bred for just one trait. All dogs carry some undesirable recessives. The goal is to avoid breeding dogs with the same undesirables.

"I feel confident that the gene pool for our breed will benefit from having carriers as well as clear dogs," says Giselle Simonds, president of the Mini­ature Bull Terrier Club of America. "We are trying to breed for the whole dog."

The DNA test also has implications for owners, even if they have no breeding plans. Owners of normal dogs don't have to peer into their dogs' eyes in dread, wondering if their dog will be one of the unlucky ones. Owners of affected dogs and carriers can be proactive in monitoring their eyes.

"Essentially PLL is a condition that's best treated when early clinical signs present themselves," says Mellersh. "Once full-blown PLL has developed, rapid-onset glaucoma can arise that can be very painful and blinding. For genetically affected dogs, we advise these dogs see an ophthalmologist every six months from the age of 18 months, so the clinical signs of PLL can be detected as early as possible. We advise that all carriers have their eyes examined by a veterinary ophthalmologist every six to12 months from the age of 2 years throughout their lives."

"Now that we have a DNA PLL test I can tell you this is a wonderful and great tool for all breeds that may suffer from primary lens luxation," says Guerrero. "Anyone who has a dog that could suffer from this painful disease will now be able to test his or her dogs and learn the outcome within weeks of submitting the test. Wise use of this test will allow breeders to avoid producing individuals destined to develop lens luxation, while still retaining many other desirable traits. No longer will we be in the dark with this devastating disease."

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