Night blindness in the Appaloosa (CSNB)

CSNB stands for “congenital stationary night blindness”. More commonly referred to as night blindness, CSNB is the name given to any disease that is typified by

a) impaired/absent night vision
b) present at birth
c) inherited
d) non-progressive 

This term does not represent a single disorder. There are several forms of CSNB in humans and other animals. The above are the features that all these unique, yet similar types of CSNB share. 

Impaired night vision is a general description. Some forms of CSNB involve extremely impaired vision, while others are less severe. They all involve some degree of lack of rod function, thus the term “night blind”.

 Is Appaloosa-specific CSNB connected to a particular coat pattern?

The 2005-06 study by Sandmeyer et al revealed that CSNB is associated with Appaloosa coat patterning of a specific type. Appaloosas with coat patterns indicating they are homozygous for LP are affected. The above diagram shows these patterns. Appaloosas that are heterozygous for LP are not affected by CSNB. Horses that are true solid non-characteristic Appaloosas, with no dominant copies of LP, are not affected by CSNB either. 

Frequently asked questions

1. What is CSNB?

CSNB stands for “congenital stationary night blindness”. More commonly referred to as night blindness, CSNB is the name given to any disease that is typified by:

a) impaired/absent night vision
b) present at birth
c) inherited
d) non-progressive 

This term does not represent a single disorder. There are several forms of CSNB in humans and other animals. The above are the features that all these unique, yet similar types of CSNB share. 

Impaired night vision is a general description. Some forms of CSNB involve extremely impaired vision, while others are less severe. They all involve some degree of lack of rod function, thus the term “night blind”. The term “stationary” is misleading and confusing, and should not be interpreted as “happens when the affected individual is standing still”. This word is a part of the technical definition, and means “unchanging”, referring to the fact that the disease is non-progressive. 

The clinical signs can be subtle and include apprehension, confusion, and even injury in dim light conditions. Affected horses may be difficult to train. Affected animals occasionally display a bilateral dorsomedial strabismus (abnormal rotation of the eyes) and nystagmus (involuntary movements of the eyes).


2. What causes CSNB - What is wrong with the eye?

The cause of CSNB is unknown. On direct and microscopic examination of the eyes there do not appear to be any physical abnormalities to account for the vision problems (Witzel 1978). It is thought that there is a physiologic abnormality in how the retina functions, specifically, in the transmission of impulses between the retinal cells. 

In order to further understand the problem we need to look more closely at how the retina works. The retina has many cellular layers that interact to process and transmit visual stimuli to the brain. Visual input comes in the form of light. When light strikes the cells in the retina it causes a sequence of electrical events that are transmitted to the brain and eventually interpreted into the image that we see. 

The first cells that respond to the light are the photoreceptors. There are 2 basic types of photoreceptors; the rods, which function best in dark conditions, and cones which function best in day-light conditions and are also responsible for color vision. 

In CSNB, the rod-pathway is affected so that vision in dark conditions is not possible. It is not actually the rods themselves that are the problem rather, the problem lies in the cells that the rods stimulate next, the bipolar cells. It is possible that the bipolar cells lack the cellular machinery required to respond to the stimulation by the rod signal.


3. How is CSNB diagnosed?

It is extremely difficult to measure quality of vision in animals as they cannot communicate with us. However, we can objectively measure the function of their retina. The most objective way we have of testing retina function is the electroretinogram (ERG). This is a test that measures the retinal cell’s electrical activity in response to light stimuli. We can accurately assess the ability of the retina to responds in dark conditions as well as bright light conditions, by varying the conditions and the stimuli used while doing the test. Normal ERG parameters are established through testing hundreds of horses under different test conditions. Horses with reduced retinal function will have changes in the ERG recordings that can be quantified. 

Normally, when a human or animal is put in a dark room vision is initially very poor until the retina begins to adapt. This is called dark adaptation; the retina actually becomes more sensitive to light as the person or animal is left in the dark. Horses with CSNB have a very characteristic abnormality in the ERG when it is performed in dark-adapted conditions. The ERG shows a downwardly deflected wave or a “negative” wave. The abnormality indicates that these horses have a block in the transmission of information through the retina such that no visual information reaches the brain when in the dark-adapted state. Effectively, they are completely blind in the dark at all times.

To test for CSNB a horse must be dark-adapted or kept in a dark environment for several minutes. This will increase the sensitivity of the rod pathway. When light is flashed into the dark-adapted eye the electrical response in a horse with CSNB has a characteristic appearance that is termed a “negative ERG”. This negative ERG is different from that of a normal horse. 

The above diagram shows a) an ERG recording from a normal horse and b) an ERG from an Appaloosa with CSNB. In the normal horse's ERG, there is a small negative deflection called the a-wave that is a result of electrical activity in the photoreceptors. This is followed by a positive deflection called the b-wave that is the result of electrical activity in the bipolar cells of the retina. In the second graph, we see the characteristic ERG recording from a horse with CSNB, dominated by the negative a-wave. Under dark-adapted conditions the b-wave is absent indicating that there is a transmission defect between the rod photoreceptor and the bipolar cell.

It should be added that some clinical signs may accompany the presence of CSNB, including apprehension, confusion, and even injury in dim light conditions. Affected horses may be difficult to train. Affected animals occasionally display a bilateral dorsomedial strabismus (abnormal rotation of the eyes) and nystagmus (involuntary movements of the eyes) (Rebhun 1984). However, since these clinical signs may be present in unaffected horses, an ERG test is required to determine conclusively whether or not the horse is affected by CSNB.

Alternatively, now that a DNA test is available for the LP mutation, the need for doing an ERG test is gone. Now all horse owners need to do is send in to the lab a hair sample from a horse they want to test. The DNA test for LP is definitive - if a horse proves to be homozygous for the mutation, it is affected by Appaloosa-specific CSNB.


4. Is CSNB in the Appaloosa connected to a particular coat pattern?

Yes – Our research has shown that CSNB is associated with Appaloosa coat patterning of a specific type. Appaloosas with coat patterns that indicate they are homozygous for LP are affected (diagram above). Appaloosas with spotted coat patterns are heterozygous for LP, and are not affected by CSNB (diagram below). Also, horses that are true solid non-characteristic Appaloosas, with no dominant copies of LP, are not affected by CSNB. 

It is important to note that some Appaloosas are born with little or no white patterning. These horses may or may not be homozygous for LP. One cannot determine what their probable genotype is by coat pattern alone. Now that a DNA test for LP is available, these horses can be tested for LP in order to identify them correctly. Horses that are homozygous for the mutation (genotype LP/LP) are affected by Appaloosa-specific CSNB. 


5. Does CSNB affect all Appaloosas?

No, only those that have inherited two dominant copies of LP. Appaloosas that are heterozygous for LP (range of spotted coat patterns) have night vision that is considered within the normal range (non-significant abnormal features in ERG’s). True solid non-characteristic Appaloosas have visual systems identical to non-Appaloosas, so are normal in all respects.

6. Can CSNB be traced to one particular Appaloosa horse, bloodline, coat pattern or pigment definition?

The 2005-06 study proved that only one variable was significantly associated with the presence of CSNB in the Appaloosa: homozygous coat pattern. The determining factor was the horse’s status with respect to LP. Those with two dominant copies were CSNB-affected, while horses with only one, or no copies, were not. No evidence for bloodline-specific inheritance was found. The horses in the study were selected because they were unrelated. Pedigree analysis revealed no significant common ancestry. 

Furthermore, since the development of the DNA test for LP, it has been possible to identify many more horses that are affected by CSNB that were born with little or no coat pattern. This is a further indication that genotype with respect to LP is the determining factor.

7. Do all Appaloosas diagnosed with CSNB have the same degree of vision at night?

Yes - As far as we can tell through our ERG studies, all horses affected with CSNB have similar impairment of night vision. Our ERG recordings in affected horses tested were nearly identical. 

 


8. At what level of lighting do horses diagnosed with CSNB experience a change in vision?

As soon as light levels drop below what you can comfortably read a book by. The change for the horse is dramatic. Below this level, a darkened room that still has enough light for you to see in and avoid all objects easily is totally black to an Appaloosa with CSNB. Likewise, outside on a moonlit night, where you can see trees, rocks and ground texture, an Appaloosa with CSNB sees nothing. The world is completely black, unless it looks straight at the moon or some other light source that is bright enough to appear as a light spot in its field of vision.

9. Do all Appaloosas diagnosed with CSNB have the same degree of vision during the day? Is their day vision the same as or different from horses that don’t have CSNB?

CSNB-affected Appaloosas likely have normal day vision, just like any other horse. Day vision is only impaired if there is some other problem with their eyes (eg. cataracts). 

Some Appaloosas have “sky eyes”, where the eye tilts upward and backward from the normal position. These horses are thought to experience distorted vision. Unfortunately, there is no way to objectively test this, however, they frequently exhibit head-tilting and other unusual behaviors, and be unusually fearful of new places and objects which suggests visual abnormalities. The technical name for this disorder is “strabismus”, and it is considered a serious defect. However, many horses that exhibit this as young animals experience self-correction as they mature, such that by the time they are of riding age, their eyes move to a more normal alignment and their vision adjusts to near-normal.

10. Is the daytime and/or nighttime vision of a horse with a blue or glass eye different than the day/night vision of other horses? Different than the day/night vision of a horse diagnosed with CSNB?

There is no association between blue eyes and visual system abnormalities. The blue colour of the eye indicates a lack of pigmentation in the iris. There may also be reduced pigmentation in the choroid (a tissue that lies below the retina). However, these horses do not show visual deficits or ERG abnormaltities. Blue eyes do seem to be somewhat more light sensitive in bright conditions (resulting in squinting or tearing), but that is all. 

11. How is CSNB inherited?

To be affected by CSNB, a foal must inherit two dominant copies of LP. If both parents have LP, there is a chance they’ll produce a night-blind foal. This varies depending on the genetic status of the parents. Spotted horses are heterozygous for LP, so they have a 25% chance to produce a night blind (LP/LP) foal when they are crossed on each other. For more examples and related information, see the Mendelian diagrams on the "Inheritance of CSNB" page.

12. If CSNB is connected to particular Appaloosa coat patterns, would CSNB be considered a genetic risk factor associated with that coat pattern?

Not exactly - the amount of patterning on the body is not the determining factor. The type of patterning is what matters, though some horses are born without patterning, yet have inherited LP. These are not "true solids" - they have or develop LP-caused traits (characteristics). 

Coat patterns that indicate the presence of two dominant copies of LP are associated with CSNB. Referring to Diagram 1 earlier in this document, you will see that fewspot, near-fewspot, large snowcap, moderate snowcap and small snowcap horses are represented, all the way down to horses born with no white patterning at all. These horses are all night blind, all equally affected. The amount of white patterning they display is not important, except that when they have moderate to large amounts of patterning, they are easier to classify correctly as being homozygous for LP. 

Horses homozygous for LP born with no coat patterning are also night blind in exactly the same way that fewspot or snowcap horses are. It is being homozygous for LP that is the determining factor, not the amount of white patterning present at birth. 

13. Can we predict it in advance?

To some extent, because we can work out the odds that particular crosses will produce CSNB-affected foals. To see what these are for various crosses, please refer to the Mendelian diagrams on the "Inheritance of CSNB" page.

14. How are horses with CSNB diagnosed? Is there a test for it?

Yes - there are two ways now to test a horse for CSNB:

1. DNA test for LP

2. ERG test

Before the development of the DNA test for LP, the only way to confirm the diagnosis was by an ERG exam. ERG stands for electroretinogram. This test is performed by a veterinary ophthalmologist – a regular veterinarian cannot do it, nor can an ocular exam alone reveal that CSNB is present. This is because the eye structure is normal when examined. In other words, all the parts are there, it is an aspect of the electrical function of the rods that is abnormal. 

Fortunately, now that a DNA test for LP is available, owners have a much less expensive method available to them, one that does not involve transporting the horse, sedation, etc.

15. Can it be determined if a horse’s actions are the result of the nature of the horse or the result of CSNB?

Yes – either by a DNA test for LP, or through an examination by a veterinary ophthalmologist. An ERG test will reveal whether a horse’s behavior is due to it not being able to see at night or in low-light conditions. 

16. Can CSNB affect other breeds of horses? Is it present in breeds that have Paint coat patterns?

So far, CSNB has been detected in a few individual horses from other breeds (eg. Paso Fino, Thoroughbred, Quarter Horse, Belgian). None of these horses were Paint patterned, nor were they Appaloosa patterned. 

However, these are not the same form of CSNB that is found in the Appaloosa - this form occurs only when the LP mutation is present. So far, it has been found in appaloosa American Miniature Horses. Since LP occurs in other breeds (eg. Noriker, Knabstrupper, POA) it is likely that they are also affected in the same manner. 

More research is needed to confirm the presence of LP in other breeds besides the Appaloosa, and also to determine the exact nature of the mutation and its relationship to CSNB.

17. Are Appaloosa horses with large areas of unpigmented skin around the eyes genetically prone to eye diseases (eg. uveitis, cataracts and skin cancer?)

Generally speaking, the risk of damage to the eye and the skin around it is somewhat related to the amount of pink skin. Appaloosas do indeed have a genetically determined tendency to have lower than normal amounts of pigmentation in the skin. Horses with that are homozygous for LP are more likely to show extreme lack of pigmentation. However, extreme mottling of skin is also something that is modified by other genes, and appears to be inherited in family lines. Skin with reduced pigmentation is at higher risk of solar burns. Sunburned skin is subject to infection and at more risk for development of skin cancers such as squamous cell carcinoma. Fly masks and sunblocks can be used to prevent sunburn. 

18. Is Appaloosa-specific CSNB the only thing that would cause an Appaloosa to have a “negative” ERG?

Yes. The “negative” ERG is characteristic for CSNB. There is no other ocular disease that causes the same type of ERG recording. Other diseases that damage the retina cause changes to the ERG but in a different way. For example, damage to the cells of the retina from recurrent uveitis can result in an abnormal ERG. In this situation, the ERG waveform may be a normal shape just reduced in size or it could be flat, but would not have the “negative” appearance of a CSNB waveform. 

19. How do we care for affected animals?

The management of horses with CSNB is easy and straightforward. These horses are already adapted to their condition, as they have been this way since birth. All they need are safe places to eat, drink and sleep during the night, and understanding owners/handlers when the horse is faced with a dark area they can’t see in (eg. trailer, dark arena, etc). 

For more information on managing CSNB-affected horses, please visit the page on this website describing "Management of CSNB-affected Horses".

20. What are the potential liability issues for breeders and registries?

Up to the present, detailed information on CSNB in the Appaloosa has not been available. Although veterinary literature refers to its presence in the Appaloosa (Witzel 1977), no one was aware of the extent of the problem, including how many horses are affected, and to what degree. 

This situation is about to change with the publication of the 2005-06 study by Sandmeyer et al. At that point in time, specific information about CSNB in the Appaloosa will enter the public domain. Though it will be some time before it is considered “general knowledge”, legally speaking, matters of liability affecting owners, breeders and registries will arise immediately upon publication of the study’s findings. 

Owners & Breeders:
It may help to think of Appaloosa breeders as being like car manufacturers. Selling cars without functional headlights has legal implications. To sell a defective product without providing the buyer with adequate information would conceivably constitute a failure to disclose, in which case the seller is liable for damages. 

According to the classification standards used in veterinary ophthalmology, CSNB fits the definition of “serious defect”. In the case of CSNB, the courts are unlikely to decide that the onus is on the purchaser to find out through his/her own effort whether a horse is affected, or a carrier, as any spotted Appaloosa is. 

Likewise, a person that is standing a stallion at stud, whether heterozygous (LP/lp) or homozygous (LP/LP), has a legal obligation to inform prospective mare owners that this stallion has the potential to sire foals affected by CSNB. 

With respect to sending a CSNB-affected horse to a training facility, failure to inform the trainer that the horse is night blind could potentially result in injury to either the horse or the trainer. To protect all parties and the horse, the owner is obliged to inform the trainer and provide adequate information to ensure that all involved are safe.

Lastly, owners are bound by federal and provincial/state laws to provide safe living conditions for the animals that are in their care. This means those they own, and those they are keeping on their property for others. Safe living conditions for CSNB-affected horses are described in full in the management appendix at this link.

Appaloosa Registries:
Once the information regarding CSNB in the Appaloosa enters the public domain, registries with mandates that include education and support of their membership would be expected to show due diligence by providing their membership with complete information on CSNB in a timely manner. 

21. Are there other causes of night blindness in the Appaloosa?

Yes. Uveitis is the leading cause of vision loss in the horse. According to research, Appaloosas are many times more likely to suffer from recurrent uveitis than any other breed:

"Spontaneous equine recurrent uveitis (ERU) is the leading cause of equine blindness, resulting from a chronic painful immune-mediated inflammation of the uveal tract in susceptible animals. ERU is thought to be a delayed type hypersensitivity reaction to self or sequestered antigens in the uveal tract. Although ERU affects as much as 10-15% of the equine population, little definitive information can be found with regard to its cause or causes. Appaloosas are eight times more likely to develop uveitis and four times more likely to develop blindness compared to other breeds." 
(Faculty Research Interests Report, University of Minnesota’s College of Veterinary Medicine, Dr. Mark Rutherford).

If you have an Appaloosa that seems to be having difficulty seeing at night, damage from uveitis may be the cause. Uveitis affects Appaloosas of any coat pattern, and frequently does lead to vision loss. Often, Appaloosas suffer an insidious form of this disease which gives no visible outward signs that it is present, so the owner may not be aware of the problem for some time. 

When the retina is damaged by uveitis, it loses some of its ability to work. Night vision is affected first, and if the uveitis recurs, noticeable loss of day vision will follow. 

The bottom line: While a DNA test can confirm whether or not your horse has Appaloosa-specific CSNB, only an ERG exam, performed by a veterinary ophthalmologist, can determine whether the lack of night vision your horse is experiencing is due to Appaloosa-specific CSNB, some other form of CSNB, or damage from uveitis or some other ocular disease.

22. How can you be so sure that the findings of the 2005-06 CSNB study apply to all Appaloosas, when only 30 horses were involved?

There a few ways to answer this question, but the simplest way is to say it is based on the laws of probability and what we know about the biology of this condition. 

The easiest place to start is to consider the statistical aspect of the study results. The fact that ten homozygotes were all affected by CSNB, while the ten heterozygotes and ten solids were all unaffected is very signifcant. Since all of the horses used in the 2005-06 CSNB study were unrelated, the likelyhood that all ten LP/LP horses in the study would have CSNB by chance alone is a very small number. That this would occur by chance is even more unlikely when you multiply the probability for all three groups (LP/LP, LP/lp, lp/lp). 

A simplified way to view the statistical argument would be to think about it like this: If you took a dice and rolled it thirty times in a row, what is the likelyhood it would land on 1 every time? This is similar to the odds that thirty randomly selected Appaloosas would end up having ERG's that correlated with their coat pattern type, and not with any other trait. 

The other part of the explanation involves what we know about the biology of Appaloosa-specific CSNB. Our previous molecular biology work showed that TRPM1 is down regulated (virtually not expressed) in the retinas and skin of LP/LP individuals. We have also shown a significant association of LP and CSNB with 3 polymorphisms in this gene (this article is available free on line at http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2052.2010.02119.x/full). 

These findings imply that TRMP1 plays an important role in night vision, and that the LP mutation causes a lack of function of this gene in Appaloosas.

Following the publication of our studies, researchers interested in vision have gone on to investigate TRPM1 in great detail. These studies have established that TRPM1 plays an essential role in on-bipolar cell function. An excellent review of this research can be found in the 2011 publicationTransient Receptor Potential Channels, Advances in Experimental Medicine and Biology 704, DOI 10.1007/978-94-007-0265-3_7, copyright Springer Science & Business Media, B.V. 2011. In particular, see Chapter 7: TRPM1 - New Trends for an Old TRP. 

Once human vision researchers became aware of our findings with respect to TRPM1 and CSNB in the Appaloosa, they began to study this gene in humans with similar ERG test results. Many mutations in TRPM1 were found in humans with CSNB, with those being homozygous for these mutations being the ones affected. This convincingly makes the case that TRPM1 is essential to night vision. In other words - having at least one normal copy of TRPM1 is critical to the function of the eye in dark conditions. With so many papers showing this to be the case in humans, mice and other mammals, the odds of the LP mutation not being the cause of CSNB in the Appaloosa are next to nothing.

In summary: The thirty Appaloosa horses tested in the initial 2005-06 study provided information that has paved the way for a major discovery - previously, the role of TRPM1 in vision was unknown and unsuspected. What is now known is that, in all mammals that TRPM1 has been studied in, individuals that are homozygous for TRPM1 loss-of-function mutations have exactly the same form of CSNB. There is no need to perform another study using more horses, as the role of TRPM1 has been revealed. We can therefore say with confidence that the LP mutation, in a homozygous state, causes CSNB.

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