Anahil Alcaraz Garcia

Understanding Congenital Stationary Night Blindness In Dogs

It is the severe darkness that blocks the eye sight when bright light appears that severe

darkness vanishes slowly. The bright light masks their potential sight and replaces it with a blur

for these affected dogs, when being around daylight. It is known as congenital stationary night

blindness (CSNB), a condition that seems to affect Briard dog breeds more than other types of

dogs. This disease makes them become completely blind in the dark. I chose this topic because I

am interested in this disease that affects many dogs, as well as figuring out a way to find a cure

or treatment. CSNB has its own mysteries as it is being seen in other dog breeds, raising concern

about what is being developed. This topic is very important, because it can lead for a new

development for humans who have congenital hereditary night blindness. This would be a next

step into animal and human health, by being able to cure or treat both humans and animals in this

disease. People who have this type of condition will want to know what is being done to improve

the ways of treating this. I feel that this topic about CSNB is one of importance for me, because I

am going into veterinary medicine. I want to be educated on issues like this one, to help me find

ways to treat animals who suffer of similar conditions like night blindness.

Congenital stationary night blindness (CSNB) is a hereditary health condition that is passed

by the carrier gene. It affects the eyes and has also been identified to be seen in the Briard dog

breed. This is caused by a mutation in the retinal pigmentation in one of the protein genes of the

eye, causing a dysfunction of the retina and the accumulation of the lipids. The retinal

pigmentation covers the area of the eye that reflects light called the tapetum lucidum. CSNB,

only affects the eye heavily when it is dark, meaning the dog becomes completely blind, but in
daylight they can see a little bit. With that being said the difference of CSNB and complete

blindness is that, being completely blind, means having no vision at all.When a dog has CSNB,

they do not have symptoms other than having absent vision in the dark. A dog’s behavior with

CSNB changes quickly when it is dark due to the retina being blocked in certain areas of the

eye.This makes them stall and be active in walking a whole lot in the dark. There are not any

treatments or a cure, as of today, for this disease. It is still being researched about the origin of

how it came about and how is it passed to another breed.

It is known that the Briard dog breed has the trait of CSNB, and that it gets passed through

birth. Now, it has been seen that this disease is being found in other dog breeds like beagles. It

has been discovered that if a dog mates with a Briard breed or another breed affected with

CSNB, it can get passed on. This results as the reason for a new dog breed being exposed a new

disease and possibly being born with this disease. In the article “A Natural Occurring Canine

Model of Autosomal Recessive Congenital Stationary Night Blindness”, it talks about a research

they did with a colony of Beagle dogs. The article went on to include how they studied these

affected dogs with CSNB, and got the results that 1:1 ratio of affected dogs and non-affected

dogs, meaning this autosomal disease passes this gene but does not always affect the animal with

it. The articles explained how they viewed that genes get passed further on to future offspring.

“Eight of the nineteen offspring produced as a result of mating between obligate carrier and

affected dogs had the CSNB phenotype. Mating between affected dogs resulted in pups all of

which had the CSNB phenotype. These results are consistent with autosomal recessive mode of

inheritance” (Kondo et al., 2015, p. 7). It is a step closer to understanding how this disease is
being found on other dogs, as it is a gene being passed from an affected breed. Many methods

are being explored to try to see what can help restore the vision for these dogs.

Although the research for CSNB is still being thoroughly looked over and analyzed, the

2001 Acland et al. provides data and information about gene therapy being the key to helping

restore vision on these affected dogs. In the article, “Gene therapy restores vision in a canine

model of childhood blindness” (citation?) it converses more about what was discovered of gene

therapy. It states, “Gene therapy has been used successfully to slow degeneration in rodent

models of primary photoreceptor diseases 5.6, but efficacy of gene therapy directed at

photoreceptors and RPE in a large-animal model of human disease has not been

reported,”(Acland, G.M., 2001, pg. 92). As they expressed their knowledge on gene therapy

helping slow down the degenerations of a primary photoreceptor diseases. They are targeting the

results collected by observing and testing it out. To do that they have to find a way to connect it

with a larger canine animal that has early and bad vision impairment, seen on patients who have

Leber Congenital Amaurosis (LCA). The article explains, “We used a recombinant

adeno-associated virus (AAV) carrying wild-type ​RPE65 ​(AAV-​RPE65​) to test the efficacy of

gene therapy in this model. Our results indicate that visual function was restored in this large

animal model of childhood blindness”(Acland, G.M., 2001, p. 92). This adds support to their

case, and also getting closer to what gene therapy can really accomplish. Briard dogs are being

researched on their retinal behavior and how it reacts to certain lights. The experimentation also

included other treatments on this research that were: ophthalmic examinations,

electroretinography, tissue processing, histology and immunohistochemistry. Each treatment

tested out was each based on a specific thing for observing and monitoring the eye as how it

develops.

From various methods being analyzed with careful consideration many things are

speculated. One thing, out of the research for CSNB, is that the delivery of RPE65 to defective

RPE cells could restore some functional vision to humans. That being said much more research

will need to be evaluated to support this claim as it could be correct. To further more support this

claim it reports, “Retinal function was improved in eyes treated with subretinal AAV-​RPE65

compared with the same eyes before treatment (Fig. 3​a​–​c​, middle). Responses from the right eye

of BR33 (Fig. 3​a​, right) had b-wave thresholds lower by approximately 4 log units than

pre-treatment and were similar to normal (Fig. 3​a​, left)”(Acland, G.M., 2001, p. 93). As this

discovery, bringing back gene therapy, it also revealed another way of figuring out a treatment or

cure for CSNB. It revealed that gene therapy has been used successfully to slow degeneration in

rodent models of primary photoreceptors diseases. The discovery on that means more tests

needed to be run for a cure to be found. With my third article I analyzed, it explained how a

homozygous four nucleotide (AAGA) deletion, representing nucleotides 487-490 of wild type

RPE65 sequence, was found only in ​CSNB ​and retinal dystrophy affected dogs; heterozygous

animals had normal and mutant alleles. What is needed to be connected from all the additional

information gathered from these articles is that CSNB is no different than human CSNB.

These articles, did support their data showing the results they got and how they put it all

together. Especially how each article recorded how these animals that were being experimented

on, and the conditions they were in. This article in specific stated that,”All dogs were housed

individually in stainless steel cages (4.6 m2). The temperature of the rooms was maintained at
15° to 25°C and the lighting was on a 12-hour light/12-hour dark cycle. The animal facilities

were at the Institute of Laboratory Animals of Takeda Pharmaceutical Company Ltd., Kitayama

Labes Company Ltd. or at Mie University in Japan,”(Kondo, M., 2015, p. 4). With the

additional data gathered, many more things need to be overly analyzed, like how can gene

therapy can be more analyzed to help with this disease, in order to find a cure. The methods and

results were very detailed and explained what was being done. What got analyzed on each article

had its own version of success. Each article got somewhere and that’s the most they can get, as it

is a research not a whole lot can be done other than taking it a step by step. I think that more

could’ve been done to the research of gene therapy. It lacked on testing it on a small canine

model. It could’ve shown a different result, and even though that article wasn’t pin pointing it

towards CSNB, it could still be resourceful to figure out if there is a difference with size.

Although, that is the only thing I would have preferred to have seen, I do agree with what was

finalized in each of the articles research.

Throughout the research, the articles I used were very resourceful and helped me gain more

information on CSNB. It gave me a more open view of how much more is thought out when it

comes to knowing what this disease does and how to get to the bottom of how to treat it. I have

found this topic very intriguing it helps me know what further steps to take on my own if ever

wanting to find a cure/treatment. It has opened the door for me to analyze the results of each

research article and investigate more to see if it can lead to a future treatment for it. With that, it

also educated me on what gene therapy does. I know that I will have to understand gene therapy

more and see how it could lead for a possible treatment for CSNB. With the information given it

will better inform me about this issue and how to analyze it in my future career job and how to
treat my patients. This will help me either on wanting to collaborate in this research and

investigate a new method for a treatment or also to help figure out how it can be applied to

humans with the similar problem.

 References

Acland, G.M., Aguirre, G.D., Ray, J., Zhang, Q., Aleman, T.S., Cideciyan, A.V., … Bennett, J.

(2001). Gene therapy restores vision in a canine model of childhood blindness. ​Nature

Genetics, ​28(1), 92-95. doi:10.1038/88327.

Aguirre, D.G, Baldwin, V., Pearce-Kelling, S., Narfström, K & Ray, K. (1998). Congenital

stationary night blindness in the dog : Common mutation in the rpe65 gene indicates

founder effect. ​Molecular vision.​ 4, 23. Retrieved from

http://repository.upenn.edu/vet_papers/39

Kondo, M., Das, G., Imai, R., Santana, E., Nakashita, T., Imawaka, M., … Miyadera, K. (2015).

A naturally occurring canine model of autosomal recessive congenital stationary night

blindness. ​Plos ONE​, 1-22. doi:10.1371/journal.pone.0137072.