Case study: Sally - Progressive Retinal Atrophy (PRA) in cats

Sally

 Sally is a 3-year-old Abyssinian cat that was rescued from a hoarding situation. She was one of 84 cats rescued. Eighty of the cats in the household were too ill or debilitated to survive and had to be euthanized. After adoption, it was discovered that Sally was Feline Leukemia positive. She is shy, but sweet, and her owners brought her in to us because she suddenly appeared to lose her sight. She began bumping into things and lost her fear of the dog. If you notice in her photo, her pupils are very dilated, and her owners had noticed this at home, too. Her regular veterinarian sent her to us because high blood pressure was suspected.

What does high blood pressure have to do with eyesight?

The retina lines the back of the eye

The retina is a thin membrane lining the inside of the eye that receives light and translates it into electrical impulses for the brain with special cells called photoreceptors. There are two kinds of photoreceptors - rods that process black and white or dim light vision and cones that process colors or bright light. If the retina or its photoreceptor cells become damaged in some way, the eye has trouble converting waves of light into signals that the brain can understand, interfering with a cat's vision.

 One of the ways that cats can lose their vision is by developing hypertension lesions in the retinas - tiny blood vessels are damaged and regions of the retina lose their ability to function as they lose their blood supply. These lesions look like bubbles in the retina. If a cat's blood pressure remains elevated for a long period of time, the retina can completely detach and lose its connection with the nerves that transmit visual impulses to the brain. Once this has happened, a cat becomes irreparably blind. If the hypertension is diagnosed and treated early, as in these photos, the retinal lesions can heal over time.

Retinal lesions appear like bubbles in the back of the eye

The same eye 2 months after starting blood pressure medication

 Notice that not only are the lesions gone, but the blood vessels appear more visible.

The first thing that we did when Sally came in was check a blood pressure reading. Her blood pressure was 150mmHg, which is a normal pressure in a nervous cat. Hypertension was not the culprit in this case. So, what could be the problem?

The next thing that happened was that Sally received a full physical exam from Dr. Demos, including an eye exam. This is what Dr. Demos saw when she looked in Sally's eyes...

Something very important is missing, here!

There are no blood vessels in this retina!
This is a characteristic feature of something called Progressive Retinal Atrophy (PRA). PRA is a recessive trait in certain breeds of cats such as the Abyssinian, the Somali and the Ocicat. Perisans and Siamese are also often at risk. There are a number of other breeds that have also been identified to carry the mutated gene in small numbers.

Other key features of this disease are a granular appearance to the retina, signs of retinal thinning, and a reduction or thinning of blood vessels. Increased reflectivity of the retina and dilation of the pupils are symptoms that owners can easily see at home. Later stages show pigment changes to the retina and a degradation of the optic nerve. These changes usually happen equally to both eyes at the same time.

Sally's pupils stay dilated, even in bright light

The most common form of PRA in cats is involved a progressive degeneration of the rod and cone receptors in the retina.The cat's eyes develop normally as a kitten, but as the cat gets older, the cat will begin to experience night-blindness and may tend to avoid stairs or darkened areas of the home. It will progress to total blindness by the age of 3-5 years. This is problematic not only for the cats themselves, but for the breeders of high-risk breeds, because often the disease is not apparent until after the age at which many cats have already participated in a breeding program. If you are interested in a purebred cat, it may be a good idea to ask your breeder about PRA and whether their cats have been genetically tested for the mutation.

Unfortunately, this is a problem for which there is no treatment. However, the good news is that cats adapt well to being without their sight due to their superior hearing, sense of smell and sense of touch (whiskers). You can read about the amazing cat, Homer, who caught flies out of the air without the aid of sight!

If your cat starts to show reluctance to move around at night, or has trouble jumping onto furniture, or starts to bump into things, it would be a good idea to have your cat's eyes checked by his or her veterinarian, as well as having a blood pressure exam performed.

Can I buy a hypoallergenic cat?

Siberian Cats are advertised as hypoallergenic cats

Is there a hypoallergenic breed?

Dr. Bailey’s quick answer: There's no such thing.

The rest of Dr. Bailey's answer: The classic allergen, Fel d 1, was originally identified as a feline salivary allergen, so the hair served as a carrier of the allergen.  I am sure the "cat allergy" syndrome is far more complicated than we even understand currently.  For instance, Fel d 1 is pleomorphic (has many forms)!  It really depends on what individual people are allergic to - different allergic folks react differently to other cats. We have sent cat owners to the E.R. after they arrived at our practice (but they live with one or more cats at home!).  Is this simply dose related, or was it exposure to different allergens?   Some studies have shown that darker colored cats seem to cause more allergic signs than lighter colored cats. Calm cats are less likely to cause allergy issues than calm cats, and pregnant or nursing females or unaltered males are more allergenic than spayed and neutered cats. Other studies have shown that males are more allergenic than females, mean females cause less reactions than nice females. I guess you could tell an allergic friend to get a calm but mean, light-colored spayed female cat.

I am allergic to cats, but I take far more antihistamines now than I did 10 years ago; and when I started working with just cats (over 20 years ago) allergies were not an issue.  I did not have a cat as a child.  I guess I can blame my mother? (Children raised with cats tend to be less likely to suffer pet-related allergies.)


What is this Fel d 1?
Originally, it was thought that cat hair caused allergies, but as more research was done, it was discovered that a protein in the saliva called Fel d 1 is deposited on the cat's skin and coat when it grooms. The protein then enters the environment when the cat sheds hairs and skin flakes (dander). This protein is the major cause of most cat allergies.

More recently, it was discovered that there are at least EIGHT different proteins that cats produce that can cause allergy symptoms, and that they are not all located in the saliva. The major allergen, Fel d 1 is even found in many different forms in many places on (and in!) the cat.

Now for some veterinary technical-speak...
These are the known feline allergens:

Fel d 1 = Secretoglobin. This molecule is pleomorphic! This is the allergen culprit in 90% of cases. Fel d 1 is found primarily in the sebaceous gland in the skin, but also in small amounts in the salivary gland, male cat urine, and perianal glands.
Fel d 2 = Albumin
Fel d 3 = A cystatin
Fel d 4 = Lipocalin. Another major allergen, a urinary protein - This is the culprit in about 60% of allergies.
Fel d 5 = Oligosaccharide galactose-alpha-1,3-galactose (alpha-gal) on cat IgA (secreted in saliva)
Fel d 6w = Feline IgM also??
Fel d 7 = von Ebner gland protein isolated from the tongue (Can f 1 homologue)
Fel d 8 = Latherin-like protein isolated from the submandibular gland (homology to Equ c 5)

Most secondary cat allergies are caused by Fel d 2 (feline albumin) or Fel d 4 (feline lipocalin).  Serum albumin accounts for about the largest number of cross-reactions between cats and other animals.

About 25% of people who are allergic to horses also react to Fel d 4.  These individuals are considered horse/cat cross-reactive.

It is known that some cats and some breeds shed less Fel d 1 than others, but little to no research exists yet as to the levels of the other allergens (2-8) in these cats.

What if I discover I have a cat allergy, and I love cats - what can I do?

Cats tend to cause more allergy symptoms than dogs because their dander is sticky and light, and travels everywhere easily. If you have cat allergies, you can try having someone who isn’t allergic brush cats daily and then clean the brush thoroughly to minimize dander. You can also use a damp washcloth to wipe down cats regularly. It is important to note that vacuums with HEPA filters will help eliminate allergens in the environment, but regular vacuums will spread them. Ask your veterinarian about healthy diets for your pets to prevent dry skin and cut down on dander.

If you do what you can to minimize pet allergens, but still have symptoms of pet allergies, you may want to see an allergist. An allergy specialist can help you pinpoint what may be causing your allergies — it may be that your allergies are worse in the winter, not because you are cooped up indoors with your cat, but because you are allergic to environmental factors that are worse in the winter when all the doors and windows are shut (such as dust mites). Your doctor can then recommend treatments such as allergy shots or medication to help control your allergic reactions. Many times, if your allergy is complex, being able to manage some of the allergens will help you tolerate the others, so you may find as you treat your other allergies, you become more tolerant of your cat.

The jury is still out on whether kittens are less allergenic than adult cats. James Seltzer, MD, a spokesperson for the American College of Allergy, Asthma & Immunology says that in general, kittens shed more allergens than cats. Although the levels seem to drop at 6 to 12 months of age, "they still cause allergies," says Dr. Seltzer. This is due to the fact that kittens are growing and shedding their epidermal layer more rapidly. Others suggest that kittens are less allergenic because many of the proteins that cause allergies are related to pheromones and sexual maturity (remember - spayed and neutered cats are less allergenic) which kittens have in lower supply. Also, kittens are smaller. It is likely that adult and juvenile cats activate different allergies because of different protein levels. Your cat may "outgrow" your allergy or conversely a cat you have lived with for a while may begin to cause more problems as he grows older - just another important reason to spay and neuter your pets; it will help keep the allergen levels down!

Allergy shots or "hyposensitization therapy" can help people with cat allergies.

Dr. Seltzer says that allergy shots (desensitization therapy - routine injections of allergens in order to decrease allergic response) are more likely to be successful for those allergic to cats than those who are allergic to dogs. "Allergy shots for cat [allergen] can be effective in as many as 65% of people, but it does take a year or two often to start working."

 The good news? Research has shown that in most cases, people tend to become desensitized to the cats that live in their own home over time. They may be able to tolerate the one cat in their home but break out with runny eyes and sniffles when they bring their cat to the vet. Research has also shown that kids raised in homes with a pet tend to have fewer allergies, themselves. And children raised in homes with multiple pets tend to have a lower incidence of allergies than those with only one pet - 66-77% lower! In addition, preliminary research seems to shows that children raised in a home with pets tend to have fewer illnesses in the first years of their lives.These studies are exciting to animal lovers, but they really don't answer the question as to whether the cats and dogs are the CAUSE of the increased health, or whether people who own pets just live a healthier lifestyle - or at least a lifestyle that is more beneficial to the immune system.

But I know I have heard about hypoallergenic cats!

Patented hypoallergenic cats?

Studies suggest hypoallergenic cats and dogs can cause just as many symptoms as the regular kind, says Dr. Seltzer. Allerca is a company that launched in 2004 to produce pets free of the major allergens, Fel d 1 (cats) and Can f 1 (dogs). Prices for cats ranged from $6,950 to $26,950 and dogs are available for $15,950. They ceased breeding these animals in January 2010 - many suspect this is because the animals still were causing reactions in allergic individuals despite the high price tag and company claims.

"The problem is that removing these proteins from the skin, saliva, and other secretions may not be enough," says Dr. James Sublett, the vice chair of  Arlington Heights-based American Academy of Allergy, Asthma and Immunology’s Indoor Environments Committee. As noted above, animals produce other symptom-triggering allergens. "Both dogs and cats have what we call minor allergens, so it's not only the major allergens," he says. "Most people have a sensitivity to minor allergens too."

 Aren't there certain breeds that are less allergic?
Siberian cats are strongly recommended by many cat enthusiasts as a hypoallergenic breed."There are no scientifically validated studies to show that any particular breed of cat, whether it's Siberian or anything else, is quote 'hypoallergenic'," says Martin Chapman, PhD. He's the president of Indoor Biotechnologies, an allergy testing company that provides the kits for most of the world's studies on allergen exposure.

As can be seen in the information provided on this site, while the Fel d 1 protein in 2 Siberian cats exists in much lower numbers than in two other cats, there is still some protein present. This test of fur allergen levels is cited by many Siberian breeder websites as evidence the breed is hypoallergenic, However, many others criticize this study, since only 4 cats were included, all the samples were submitted by a Siberian breeder, and one mixed breed cat tested with allergen levels of over 60 times higher than the highest allergen level tested in cats anywhere else (62,813 micrograms). The fact remains that many people report that they are less sensitive to Siberian cats than the general population of cats at large. However, individuals with allergies to other animals (especially horses and rabbits), or food allergies to eggs and pork meat often react to low Fel d1 Siberians.

Siberian Cat: Triple Grand Champion, Karat

A not-for-profit association of breeders, (Siberian Research Inc), was founded in 2005 to study allergen levels and genetic diseases in the Siberian breed. As of March 2010, fur and saliva samples from over 300 Siberians have been submitted for analysis, many directly from a veterinarian. Salivary Fel d1 allergen levels in Siberians ranged from 0.08-27 mcg per ml of saliva, while fur levels ranged from 5-1300 mcg. The high-end of these ranges is consistent with results from prior studies, though the low end is below expected results. All Siberians tested were found to produce some Fel d1, with the highest levels being found in Siberians that have silver coloured fur. About 50% of the Siberians tested were found to have Fel d1 levels lower than other breeds, while under 20% would be considered "very low". Within the low group, males and females had comparable allergen levels.

Other breeds that are variously considered to be "hypoallergenic": Balinese, Bengal, Burmese, Colorpoint Shorthair, Cornish Rex, Devon Rex, Javanese, Ocicat, Oriental Shorthair Russian Blue, Siamese and Sphynx

Devon Rex

Some of these breeds have fewer hairs per follicle or even lack hair completely, which provides less surface area for allergens to cling to. Other breeds also have lower Fel d 1 proteins, like the Siberian cat. There is no guarantee that a hypoallergenic breed is going to be a cat that you can tolerate, if you have allergies.

While little research exists about allergen levels in other breeds, or about minor allergen presence in any breed, this information does seem to suggest that some people with allergies may find some breeds more tolerable versus other breeds. Definitely, this is an area that could use much more research so that cat lovers with allergies can enjoy feline friendship with the rest of us crazy cat people!

Further reading about hypoallergenic cat breeds:
Pet MD

Cats of Australia

Catster

Does An Apple A Day Keep the Veterinarian Away? - Feline Health Myths Part 4

Myths: 

1) All orange cats are male.

2) All calico cats are female.

3) Rare calico males are worth a lot of money, and cannot reproduce.

Rainbow and CC - a cloned cat and her "mother"

Reality:  Feline coat color genetics can be very confusing. One of the great scientific experiments 10 years ago was that of cloning a cat. Rainbow was her name, and CC (Copy Cat) was her clone - they have the exact same DNA, but they look quite different. Rainbow is a calico and CC is a brown tabby and white cat. This just helps to illustrate how complex this situation is! 

1) Orange cats can be male or female.

First, a little about genes: The gene for orange coat color is classified as a sex-linked gene because it is carried on a sex chromosome. The genes that make us male or female are on the X- and Y-chromosomes. An X from the mother and an X from the father makes XX or female. An X from the mother and a Y from the father makes XY or male. The male is the one who determines the sex of the offspring.

Orange tabby cat with a typical "M" marking and faint leg stripes

The orange gene doesn’t add orange hair coloring to white fur, it actually changes black pigment into a reddish pigment. The orange gene is carried only on the X chromosome. Since a normal male has XY chromosomes, he only needs to inherit one orange gene for him to be an orange cat. A normal female is XX genetic makeup so she must inherit two orange genes to be an orange cat. If she inherits only one orange gene, only some of the black color will be converted to orange, so she will be a patchy orange and black coloration called a “tortoiseshell” or “tortie”.

Also, if you look closely, all orange cats have tabby markings. Sometimes the tabby markings may be limited to just the “M” above the eyes, or stripes on the legs or tail, but they are always there. They are also visible in the orange areas of tortie cats. This is because the gene that turns off tabby to give solid color cats does not work on the orange color.

Since females must have two orange genes to be a pure orange cat, they are less common than male orange cats, but they are not considered to be rare. If two orange cats breed, they will have orange offspring, because both the X-chromosomes in the mother and the X-chromosome in the father will all have the orange gene.

The genetics of orange or ginger coat color is explained in more detail in Tortoiseshell and Tri-Colour Cats (orange is caused by the same gene as tortoiseshell).

Ginger, our favorite tortoiseshell

2) Tortoiseshell and calico cats can be male or female, too! 

How can this be, since we just learned that of the male has the orange gene, all his black color will be changed to orange?

First, "tortoiseshell" refers to a mottled coat pattern of orange and black with very little white. This coat pattern can also be grey or blue-ish and cream, but is then called "dilute tortoiseshell".

Cleo, a lovely calico

Calico coat patterns have large areas of white with distinct orange and black patches. Interestingly, the Japanese word for calicos is mi-ke and translates into "triple-fur" - a very apt description!  Calicos can have single-color patches or tabby striped patches. If they have stripes, they can also be known as "patched tabbies", "tortie tabbies" or "torbies". Calicos can also have the dilute blue or grey and cream coloring.

There are three ways that a male cat can end up with calico coloration:

1)     Chimerism – Something happens during the pregnancy to cause two embryos to fuse together. If one has genes for black coat color and the other has genes for orange coat color, and one or more of the embryos are male, the result may be a tortoiseshell or calico male. This scenario is most common in animals that give birth to large litters…just like cats. These cats will be fertile, however, their offspring will not be calicos or tortoiseshells, since they can only pass on one X-chromosome at a time.

2)     Klinefelter Syndrome – XXY chromosomes. Since it has a Y chromosome, this cat will be male, but since it has two X chromosomes, it is able to have one X-chromosome with the orange gene and one X-chromosome with the black gene. These cats will be sterile.

3)     Somatic Mutation – During development, an orange male develops a black patch, which happens similarly in human babies with port wine stain birthmarks. These cats will be fertile. 

3) While calico and tortoiseshell males are rare, and scientifically interesting, they are not really more valuable than other cats, even if they are fertile males.  

The offspring of these cats will not have any more likelihood of being calico males or male tortoiseshells than any other cat, so their total "worth" is usually as much as their breed is worth. For example, a Grand Champion purebred calico male Persian will be worth more money than a stray calico male off the street. The genetics of tortoiseshell males is explained in more detail in Tortie Tomcats.

There is, however, a superstition is that these cats are good luck.

Of course, we all know that the true worth of a cat is in its personality and affection, and the joy that it brings to our homes - male or female, calico or not!