Retinitis Pigmentosa otherwise tapetoretinal degeneration of the retina is a rare disease, occurring with a frequency 1 out of 4000 births. In Poland there is about 15,000 people suffer from it although no accurate statistics are available.

The essence of the disease is the disappearance of photoreceptors that is, cells capable of processing visual signals into electrical signals transmitted to the brain. There are two types of photoreceptors – rod cells and cone cell. Atrophy starts with rod cells, which are responsible for seeing at dusk and in the dark. As more cells die, patients’ vision narrows up to maintaining the island of central vison consisting mainly of cone cells. Cone cells are photoreceptors responsible for the ability to see details, colors, enabling us to read and perform precise activities. In the majority of patients with Retinitis Pigmentosa cone cells start to die in a later age, with an exception of one type of a Retinitis Pigmentosa otherwise called Rod – Cone Dystrophy where cone cells die first and later rod cells.

In Retinitis Pigmentosa, beside the photoreceptors atrophy, we encounter subcapsular cataract in 39-72% of the cases, and in 30% of the cases a hearing impairment not connected to the Usher Syndrome.

Due to the nature of the disease, the first difficulties appear in childhood, especially at dusk and at night. Parents notice that with a little light a child cannot find certain objects or perform certain tasks. For example a child cannot find a way to the bathroom at night in a strange place.

The most severe form of Retinitis Pigmentosa is Leber’s congenital amaurosis, in which both types of photoreceptors – cone cells and rod cells are attacked simultaneously.

Ways of inheriting

Retinitis Pigmentosa is a group of genetically transmitted diseases, although there are sporadic cases where no one of the ancestors was ill before. Retinitis Pigmentosa can rarely be part of syndromes that is situations in which the eye symptoms are accompanied by other diseases. The syndromes most often accompanied by Retinitis Pigmentosa is the Usher Syndrome (eye symptoms co-occur with partial hearing loss), the Bardet–Biedl syndrome and the Refsum disease.

There are 4 ways of inheritance and all of them may occur in Retinitis Pigmentosa:

1. 1. Autosomal dominant, ADRP, where regardless of the genetic material of the other person 100% children will be affected.
   2. Autosomal recessive, ARRP, where there are 50% risk that the child will become ill.
   3. Linked to X chromosome, XLRP and two-hybrid, where the women are the carriers and mostly men get ill. It is believed that about 20% of women can nevertheless get sick, although the disease has a milder course than with men.
   4. Mitochondrial and non-genetic, so called sporadic – in those cases it is difficult to define the percentage in which the disease is transferred onto the offspring. Retinitis Pigmentosa is a first case in a family in 10% to 40%.

To understand how difficult it is to diagnose and treat Retinitis Pigmentosa is to realize that so far 150 genetic mutations have been discovered.

So much variation in the way of inheritance makes it very difficult to diagnose, because even genetic testing does not guarantee answers to all the questions. Partially it is due to the costs of testing such a big number of genes, and partially due to inability of isolating all damaged genes, because – as I wrote before – in Retinitis Pigmentosa, spontaneous gene mutations are possible.

What are stem cells?

Many myths and inaccuracies surround stem cells. First of all we need to understand that stem cells are not one kind of cells but many. Among stem cells there are undifferentiated embryonic cells and mesenchymal stem cells, which are currently intensively studied and used mainly in clinical trials and scientific experiments. Mesenchymal stem cells can be grown from three sources: from bone marrow, body fat or from the umbilical cord, specifically from the connective tissue surrounding blood vessels called Wharton’s jelly.

All techniques are based on isolating stem cells and then stimulating its multiplication, independently from the type of tissue used to produce them. For example it takes two months to grow stem cells from Wharton’s jelly from the moment of the umbilical cord extraction to the final product.

It needs to be stressed that in case of the mesenchymal stem cells there are no problems of ethical nature, as is the case of undifferentiated human embryonic cells.

It is also possible to transplant cells between different people without a risk of a transplant rejection. It is because stem cells are nearly invisible to the immune system.

In what way a stem cell therapy can help patients with Retinitis Pigmentosa?

Mesenchymal stem cells should be treated as an additional secretory gland, which under certain conditions produces substances that improve blood circulation, acts anti-inflammatory and also promotes regeneration. Mesenchymal stem cells have antineoplastic effect. Beside a therapeutic effect, based on a change of the cellular environment and directing affected cells toward proper functioning, stem cells can also transform into other cells. It needs to be stressed that quantity of cells, which transform into missing cells is small. Animal testing has shown that newly created cells have properties of the missing nerve cells and are capable of secretion of typical to them substances. It is not known whether newly created cells are able to create synapses or connections between nerve cells. In case of complex tissues, such as retina, recreating all the cells’ layers is not possible at the present stage of knowledge. For now we concentrate our efforts on the most affected layer of photoreceptors and located under it the retina’s dye epithelium.

In regenerative therapy of the retina there are also attempts of implanting stem cells transferred into photoreceptors, replacing damaged cells with new ones. Outcomes of those experiments are not available yet, although a problem is a survival of the new layer of cells and its connection with host cells. In this case the difference is based on a way we use stem cells. After isolating stem cell, we grow from it for example – photoreceptors and only then transplant them under the retina.

How is it done?

Stem cells can be transplanted into different parts of the eye. All methods require surgery under operating room conditions. In some of the cases a surgical removal of the vitreous is necessary. Stem cells can be transplanted into:

– vitreous chamber,
– subretinal space,
– in front of the edema,
– in front of the optic nerve,
– into the muscle cone that surrounds optic nerve connecting the eye with the brain.

Even though there are no exact tests on stem cells survival time in human eye, it is believed that they survive for a few months. During that time they produce regenerative substances, gather where inflammatory processes are, and influence cells’ metabolism.

Switching damaged cells to new metabolic pathways improves their functioning, as well as stops degenerative processes in tissues surrounding damaged cells.

Future?

Although in most patients the vision improves, we do not know how long it will last. Undoubtedly there is a temporary stop of retinal degradation. But the future of cells’ therapy will depend on a discovery of a way to control connections between different types of cells, which will allow recreating such complex structures as retina. Undoubtedly a creation of safe ways of implanting stem cells into the eye and keeping them alive, so they can become part of the new host’s body, will be needed.

Impossible to treat with medicines. It will happen to everybody who lives long enough. According to the World Health Organization it is the most common cause of blindness in the world. But a cataract removal surgery is a fast and very effective ophtalmological treatment with almost 100% chances of success. There’s nothing to be scared of! Moreover, a new synthetic lens can be better than the one we’ve got since birth.

Cataract is an opacification of the lens which prevents the light to penetrate the inner eye and as a result causes a loss of vision. In antiquity people believed it was caused by a blockage of a special fluid flowing from the brain to the eye – like in famous cataracts on the Nile. Cataract is an inevitable part of growing old. Why do some people contract it earlier than others? Because of the biological clock which makes different body parts grow older with a varied speed. There is also congenital cataract, present in 1 in 250 newborns.

The most advanced form of cataract is mature cataract – a person suffering from it hardly sees any light.

How to treat cataract?

Surgically only. Eyedrops that slightly supress a development of cataract exist on the market but they don’t revert already existing changes. Despite the fact that the cataract removal surgery is the most common ophtalmological treatment in the world, according to the WHO over 20 million people can’t see due to untreated cataract. This number will grow because the society is getting older.

How does a cataract removal surgery look like?

Firstly, the eye is anaesthetized locally. Then the surgeon makes a 2 mm cut in the cornea and cuts a round opening in the frontal capsule of the lens, through which the cloudy lens will be removed. Before removal the lens will be divided into smaller parts using a procedure called phacoemulsification. The device used in this procedure can be compared to a vacuum cleaner which simultaneously grinds down and sucks out parts of the lens. The aim of this treatment is to remove the content, i.e. the cloudy lens, while retaining its packaging – the capsule.
After removing the old lens, a new synthetic rolled up lens is being implanted in its place and uncurled. This way a new content is being placed in the old packaging. A patient is fully conscious while the treatment is carried out but the surgery is entirely painless.

Lenses that work miracles

New synthetic lenses try to meet our eyes’ needs as much as possible and equal nature. All of them, like our natural lens, have filters which protect the retina from harmful effects of UV rays.

It happens though that synthetic lenses outclass our natural ones. For example those equipped in additional UV filters – useful in case of age-related macular degeneration and for people with retinal or choroidal nevi.
Lenses which correct significant sight defects are also very popular. Thanks to modern lenses we can now correct a sight defect of -20 dioptres! Complicated defects, such as astigmatism, also don’t constitute a problem. They can be corrected thanks to special toric lenses. Can we then say that artificial lenses are better than natural ones? Yes and no. Yes, because they can work miracles in case of significant sight defects and no, because they are not able to accommodate.

Accommodation is a unique feature of our own lens. It allows us to see at varied distances because our lens changes its thickness accordingly. Unfortunately this ability doesn’t last forever. It starts deteriorating when we are about 40 years old and from then on it gets worse. This is when we start having problems with reading or working on a computer. But even then new opportunities arise – we can use pseudo-accommodative lenses. They will not bring back our youth but they will allow us to see from two or even three different distances, like bifocal glasses.

But that’s not the end of miracles. In some clinics, such as the Retina Ophtalmological Hospital, we implant lenses facilitating laser therapy for patients with lattice degeneration and diabetes. Sometimes we choose special lenses that magnify the picture and facilitate reading for people with macular degeneration.

National Health Service-funded treatments use the most basic lenses and you need to pay for the more complex ones. It’s better to implant them in private clinics where ophtalmologists match them to your needs.