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Coat colour link to appaloosa night blindness explored

The horses are in trouble.

That’s all Sheila Archer could think when she awoke with a start at 2am during an early spring storm in 2003. As rain pelted against the windows of their farmhouse south of Moose Jaw, Saskatchewan, Archer and her husband hurriedly dressed and headed outside into the pitch-black night.

Their four Appaloosa mares should have been standing on the well-protected, south side of the barn – but not one horse was there. “We went out to our north pasture, and there they were: standing on a hill, shivering and hypothermic in the cold rain,” recalls Archer.

What stood between the horses and shelter from the storm was an S-curved, dirt roadway that crossed over a culvert draining the farm’s dugout. When the couple moved their mares to the farm months earlier, they had run electric fence on either side of the wide causeway – a precaution that posed no problems for the horses in the daylight.

“But at night and in the middle of that storm, they would not cross the causeway to get to the barn. They finally crossed but only after we talked to them, put on their halters and led them through to the other side,” says Archer. “And that’s when I knew my horses couldn’t see in the dark.”

Nearly three years after that memorable night, Archer now knows with certainty what causes her horses’ vision to disappear after sundown. First described in the late 1970s, congenital stationary night blindness (CSNB) is thought to be a hereditary, non-progressive condition found in some horses. All reported cases have involved Appaloosa horses so far, but because little is known about the disease, it may also affect horses of other breeds.

Other than Dr. D.A. Witzel’s initial CSNB research in Appaloosa horses nearly three decades ago, very little information about the disease is available in veterinary literature. In fact, one of the “bibles” of veterinary ophthalmology textbooks contains only one paragraph describing the disease, says Dr. Lynne Sandmeyer, a veterinary ophthalmologist at the University of Saskatchewan’s Western College of Veterinary Medicine (WCVM).

Few words are written about CSNB in horses – but Sandmeyer thinks the condition may occur more often than horse owners and veterinarians think. Since most owners don’t have much interaction with their horses after dark, the condition’s symptoms – such as a horse showing some anxiety in darkness or closely following another pasture mate at night – can go unnoticed.

“Under normal circumstances, affected horses can cope with the condition because they’re born with it – it’s not like something suddenly changes in their lives. They just think that’s the way the world works: at night, the lights go out and they can’t see,” explains Sandmeyer, who is leading one of the most comprehensive research investigations of CSNB in Appaloosa horses ever undertaken.

Project sheds light on eye disease

For the next two years, the College’s Equine Health Research Fund is providing financial support for Sandmeyer’s research team whose members include veterinary ophthal-mologist Dr. Bruce Grahn and Dr. Carrie Breaux, a veterinary ophthalmology resident.

In the first phase of the study, the research team will conduct detailed eye examinations on 30 Appaloosa horses as well as on 10 Arabian horses (the study’s control group). Since scientists suspect that CSNB is caused by a problem during the process of transmitting information from a horse’s eyes to its brain, the project includes a detailed series of electroretinographic (ERG) testing on each horse.

“The ERG testing will confirm the disease in horses, plus it will also allow us to study the exact electrical responses and to see if we can pinpoint where the transmission problem occurs,” says Sandmeyer. “We’ll examine the horses’ eyes to check for any abnormalities, and we’ll test whether any of the animals are nearsighted or farsighted since anecdotal reports have suggested that CSNB-affected horses are nearsighted.”

The research team will conduct more detailed anatomical studies of affected eyes, then do further immunohistochemistry testing to try and pinpoint any physiological abnormalities.

“We’ll also be collecting blood from the horses so at some point, we can investigate the gene for the disease,” adds Sandmeyer, who says the ultimate goal is to develop gene therapy for CSNB.

“If nothing is morphologically wrong with the horse’s retinal cells, we may eventually be able to provide those cells with the material that they need to activate the physiological process and allow them to work at night,” explains the researcher. “That’s many years down the road, but someday, we may have the means to help these horses.”

The WCVM study is also part of a larger, genetic research initiative called the Appaloosa Project whose research collaborators are striving to identify and isolate the main genes responsible for Appaloosa patterning, and to investigate key physical traits associated with these genes. For instance, one possibility is that the occurrence of CSNB is associated with a certain type of coat pattern found in the Appaloosa breed – a hypothesis based on anecdotal reports from horse owners and on results from genetic studies conducted by the Appaloosa Project’s researchers. Last fall, someone who has personal experience with CSNB – Sheila Archer – presented that hypothesis to WCVM’s team of veterinary ophthalmologists.


Besides being an Appaloosa breeder, the phenotype (physical traits-based) researcher co-ordinates the North America-wide Appaloosa Project from her home near the small rural community of Spring Valley, Sask.

In 2003, Archer was involved in a genome scan conducted by Dr Rebecca Bellone, a genetic researcher from the University of Tampa and one of the Appaloosa Project’s collaborators. That scan mapped the location of a gene called leopard complex or Lp – the gene responsible for “turning on” the Appaloosa spotting pattern – to a region on equine chromosome 1.

When geneticists have isolated a gene to a section of a chromosome, they still need to identify the actual gene within the region that’s responsible for the trait they’re studying. One method used to find the target gene is the “candidate gene” approach.

“Since scientists have extensively mapped the genomes of the human and the mouse, we compared the region of equine chromosome 1 that Lp resides in to matching sections of human and mouse chromosomes, and we found some obvious suspects involved in pigmentation,” explains Archer.

One candidate gene for Lp is oculocutaneous albinism type 2 (OCA2) that’s associated with very low levels of pigmentation and night blindness in humans. In mice, the most common form of this gene is associated with a totally white appearance and pink eyes. But scientists have identified many different identified versions of the gene – some of which cause a mottled, roaned coat pattern. After Bellone identified OCA2 as a candidate for the Lp gene, Archer began investigating phenotype-based information about Appaloosas that would help to confirm whether or not Lp is a mutation at the same locus or “genetic address” in the horse as OCA2 is in humans.

During her research, she collected stories from owners whose Appaloosa horses had shown signs of blindness in the darkness or dim light. In most cases, affected horses were “few spot” or “snowcap” Appaloosas – the breed’s descriptions for relatively spot-free coat patterns. These same patterns occur on horses that have been confirmed as homozygous (having two identical genes at the corresponding position of similar chromosomes) for the Lp gene. Those stories intrigued Archer because the symptoms were similar to her own experiences with her horses’ vision. The coat pattern descriptions also fit her Appaloosa mares – all of which have few spot or snowcap patterning.

Curious, she brought two of her horses to Dr. Bruce Grahn at WCVM’s Veterinary Teaching Hospital for eye examinations. She also brought along her suggestion that CSNB in Appaloosas may be associated with certain coat patterns – a possibility that became more plausible once Grahn confirmed that Archer’s horses had CSNB. “After Dr. Grahn finished examining my second horse, he said, “I think we’ve got something here,’ and I remember feeling really excited about what this could mean for the Appaloosa Project – that maybe we had our gene. At the same time, I felt strange. I was convinced that my horses had CSNB before I even came to Saskatoon, but as I stood there supporting my very drugged horse, it still upset me to know with certainty that she couldn’t see at night.”

But rather than hiding that fact, Archer believes she and other Appaloosa breeders and owners need to know more about the disease to protect their horses as well as the people who work and interact with CSNB-affected animals.

“It’s a lot easier on the horse if people have a better idea of what’s going on, so yes, I would love veterinarians, breeders and owners to know more about the condition. Then we can avoid potentially dangerous situations, we can learn how to better manage these horses and we can have a better understanding of how this condition may affect their behaviour and reactions to everyday things.”

“CSNB-affected horses are healthy, viable and useful horses,” adds Sandmeyer.

“This is a manageable condition, and if owners know their horses are affected by this disease, they can put measures into place that keep their horses – and their families – safe.”

 

Spots and CSNB: association?

To test whether CSNB is associated with the gene responsible for the Appaloosa spotting pattern, Archer is helping the WCVM research team track down 30 purebred horses – all with different pedigrees.

Researchers will select horses that display three different types of coat patterns: few spot or snowcap (patterns with few or no spots), spotted leopard and spotted blanket patterns (plentiful spotting) and “true solid” Appaloosas, showing no coat pattern or any signs that Lp is present (horses that have Appaloosa parents but look like normally pigmented horses). Besides determining if there really is an association, the study will also answer researchers’ questions about whether there are variations in the severity of the disease among horses or changes in affected horses’ day vision.

If all 10 of the project’s few spot or snow cap-patterned horses are night blind, there are two possible explanations. It could mean that the Lp gene is also the causative mutation for CSNB in the breed. Or, another possibility is that the Lp gene lies extremely close to the gene containing the causative mutation for CSNB – so close that the two genes are linked.

Either way, developing a test for Lp would be equivalent to developing a test for CSNB in Appaloosas, points out Archer. She adds that if the WCVM research team finds a direct correlation between CSNB and few spot and snowcap patterning in Appaloosas, it could save the Appaloosa Project’s researchers time in the hunt to discover the identity of the Lp gene.

A better understanding of the condition’s genetic makeup would also help veterinary ophthalmologists like Sandmeyer eventually develop genetic therapy for CSNB.

While researchers wrestle with this puzzling disease, Archer’s Appaloosa horses continue to graze, sleep and play in a world they can’t see after dusk.

But some changes have occurred since that rainy night in 2003: the horses now spend their nights in a dimly lit barn and they’ve all foaled babies inside. Archer also brings her CSNB-affected horses in during thunderstorms since sudden flashes of lightning seem to disorient them.

“Sure, there are some management issues, but it’s really not that hard. The only differences in my life is that I have to clean the barn every morning, and I pay a larger electrical bill for my barn,” says Archer.

“But for me, I don’t think it’s a very big price to pay. A few chores and a little bump on my electrical bill are worth it if I can have these wonderful creatures in my life.”

 

Lost in translation

Look deep into the eyes of a horse affected with congenital stationary night blindness (CSNB) and you’ll see nothing but liquid pools of colour and light. Even specialists like WCVM’s Dr. Lynne Sandmeyer – equipped with the latest in ophthalmic technology – haven’t discovered anything unusual about the retinas of an animal affected with the condition. That’s because the actual problem that causes this type of blindness is virtually invisible – occurring somewhere during the process of transmitting information from the eyes to the horse’s brain.

As Sandmeyer explains, cells called photoreceptors are responsible for transmitting information from the retina to the brain. Cone-shaped photoreceptors take care of colour and day vision, while rod-shaped photoreceptors are responsible for vision in the dark.

Normally, rod photoreceptors pick up the light that comes in the eye and transmits it into an electrical response. With the release of neurotransmitting chemicals, the rod photoreceptors relay the electrical response through other processing cells until it eventually reaches the brain where the information is transformed into an image.

But in a horse diagnosed with CSNB, something stops this neurological “Pony Express” from happening normally: “We know the rods are there, and they’re not abnormally shaped – but somewhere along the line, the information is dropped or not transmitted properly,” says Sandmeyer.

Those transmission problems are mirrored in electroretinograms that are used to make a definite diagnosis of CSNB. After keeping a horse in the dark for at least 20 minutes, a veterinary ophthalmologist conducts a series of tests using electroretinography (ERG) to pick up the electrical information of photoreceptors and other cells in the horse’s retina as they respond to light.

“A normal ERG consists of two waves showing the responses of the photoreceptors. The A-wave has a downward peak that goes down a little bit, and then there’s usually a slower, upward peak that’s called the B-wave,” explains Sandmeyer. “In a horse with CSNB, that first A-wave shows up, LOST in Translationbut instead of a B-wave showing up, the A-wave just continues to go down. In other words, the information is dropped so there’s no image.”

Will scientists ever “see” what causes CSNB to happen? The WCVM-led investigation of the disease’s characteristics may uncover some clues, but Sandmeyer suspects it will be a long process. “One of the next steps we can take is to look at the physiological differences between the eyes of normal horses and the eyes of horses diagnosed with CSNB. With the use of immunohistochemistry, we could try and pin down whether it’s the transmitters, the transmitter receptors or other aspects of the retina that aren’t working.”

She adds that this could be another way for genetic researchers to identify the gene responsible for the disease and its location in the horse’s genetic makeup: “If we find out that CSNB occurs because a certain neurotransmitter is not there, then we would know that the genetics involved in developing that neurotransmitter is the source of the problem. It’s simply taking a different approach to finding the gene responsible for CSNB.”

Solving the CSNB puzzle in horses is valuable to veterinary medicine, but the information may also help researchers gain a better understanding of the equivalent disease in humans. As Sandmeyer points out, the ERG abnormalities that show up in the eyes of CSNB-affected horses are similar to the results recorded in humans affected by the Schubert-Bornshein type of CSNB.

“If we identify the CSNB gene in horses, it could potentially benefit the work of researchers involved in human CSNB studies by narrowing down their options. Just as we use human research, they could test whether our gene is causing the same disease in humans.”

• Appaloosa study reveals gene for blindness, colour 4.9.08

 

Article reprinted with permission from Western College of Veterinary Medicine and the Equine Health Research Fund. It first appeared in Horse Health Lines, in 2005.

Article first published on Horsetalk.co.nz in October, 2007.

 

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Comments (3)

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  1. Jennifer says:

    Hello,
    I am curious to know whether or not a few spot can sire a colt with night blindness if he is crossed with a non-appaloosa?

    • Donna says:

      I’ve been breeding appies for many years and currently stand a few spot stallion. I was unaware of Night Blindless until 15 years ago when a friends few spot stallion had got tangled in wire in the night. The vet had said he had either a brain tumour or Moon blindness and would need to PTS. Well I went to see him in the daylight and he was showing no signs of having any seeing issues. We decided to test all 11 of our appies. From solid half bred to snowcap full bred. At dusk with white and black buckets then in the dark, then with torchlight. Our conclusion was-pure bred fewer spot/pink skin homozygous could see nothing, pure bred blankets/leopards only white buckets at dusk/dark, but interestingly part breds and marbles/roans seemed to see all. You make allowances……don’t leave strange things in fields, don’t change environment near dusk, be aware trying to load into a darker place/lorry/trailer. Don’t ride them in the dark! Never had so much as a cut on any, but plenty of squashed feed buckets! I now only cross my stallion with solid mares to get my spots.

  2. Tiffany J says:

    I have a registered snow cap appy mare. She is great but always is in my space at dusk/night she tries to walk on top of me. Is near to impossible to load if it gets dark. Finally figured out the she was having a hard time seeing. I have added extra lights on the barn & lights inside my trailer. It has really helped at home I try & thinkabout lighting now when riding or traveling. It’s been a few years has not seemed to progress or Change.

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