Stem cells

Stem cells are a special type of cell, which under the right conditions can be encouraged to grow into any other type of cell in the body, including retinal cells (rods, cones and retinal pigment epithelial cells).

In lower vertebrates, such as frog and newts, the eye is able to repair itself after injury. Unfortunately, the human retina cannot repair itself. The mature photoreceptors and retinal pigment epithelial cells are unable to divide and produce replacement cells in the event of cell death.

Stem cell therapy for the eye involves taking either the stem cells themselves, or retinal cells which have been derived from stem cells, and transplanting them into the retina. The aim is that these cells will then replace damaged areas of the retina and start functioning as the original cells would have done to restore aspects of sight. Stem cells are currently under investigation in early phase clinical trials to determine their potential to repair areas of the retina where cells have otherwise been damaged or lost due to progressive retinal degeneration.

Should I go abroad for stem cell treatments?

Types of stem cell

Different stem cells exist at various time points during an individual’s lifespan, from conception to old age.

Broadly speaking, embryonic stem cells have the capability to generate any cell type in the body, while adult stem cells are often restricted to generating a certain tissue type e.g. heart muscle cells or liver cells.

More recently, scientists have found ways to turn an adult cell (usually skin) back into an embryonic-like stem cell. These are called induced pluripotential stem (iPS) cells and are playing an increasingly important role in many areas of medical research.\

iPS cells derived from the skin of somebody with inherited sight loss will contain the mutation that caused their retinal condition. If these iPS cells are persuaded to develop into retinal cells in the lab, researchers have an ideal cellular model for studying disease processes and experimenting with new treatments.

Gene editing techniques could be used to take this into clinical use, by correcting the mutation in the iPS-derived retinal cells and then transplanting them back into the eye to restore the damaged retina. However, the effectiveness of this approach has yet to be established.

Past developments in stem cell research

“Seeing with our skin” was created by Dr Mariya Moosajee, Consultant Ophthalmologist at Moorfields Eye Hospital and Senior Lecturer at UCL Institute of Ophthalmology, specialising in Genetic Eye Disease, and Meike Walcha-Lu, film-maker for the NIHR Moorfields BRC.

Stem cell treatment clinics

There are clinics and companies abroad offering stem cell treatments with a very high price tag. Currently stem cells are not approved as a treatment for the retina or optic nerve anywhere in the world, and at this time there is no scientific evidence or published results of previous clinical trials that support the use of these treatments.

With stem cell injections can come a risk of eye infections, further damage to the eye and even a risk of tumours in the eye. The therapies these companies are offering are likely to be unregulated and untested for safety and benefit. It would be considered ethically unjustified for specialists here in the UK to administer these procedures. They could do harm that might jeopardise the potential to benefit from other treatments in the future.

The website About stem cells offers more information about the issues surrounding commercial stem cell treatments.

It’s important to interrogate the science and ask “Is there evidence?”. You have to be incredibly cynical.

Rob Henderson, ophthalmic surgeon

Previous developments

A high power image showing the position of a single transplanted photoreceptor cell (green) making new connections with bipolar cells in the recipient retina (cyan).

There have been a number of significant advances in photoreceptor replacement therapy in the last decade. In 2006, UK researchers at UCL Institute of Ophthalmology identified a critical stage of development at which immature retinal cells can be transplanted successfully into the retinas of mice with retinitis pigmentosa.

More recently (2013), the same team at UCL Institute of Ophthalmology provided the first evidence that these transplanted cells make connections with the retina into which they are placed and moreover are capable of restoring vision in a mouse model of stationary night blindness (See video below).

Restoring vision in night blind mice (UCL)

Mouse Embryonic Stem Cells Grown in a 3D Culture System to Form Immature Retina. Multiple photoreceptor precursors (immature photoreceptors) are seen (green).

An important question is whether different types of RP are equally amenable to cell therapy and whether it is possible to treat very advanced degeneration. In a Retina UK-funded study, researchers at UCL demonstrated that it is possible to achieve effective levels of transplantation into a number of models of RP, including those undergoing rapid and severe degeneration. These results show that cell transplantation could potentially benefit many patients with various diseases that have different genetic causes. However, it may still be necessary to manipulate the host retina to improve transplant success.

An important finding from the work published in 2006 was that the donor cells have to be at a very specific stage in development at the time they are transplanted. They need to be photoreceptor ‘precursor cells’. These can be thought of as ‘baby’ photoreceptors. They are destined to become photoreceptors but have yet to fully mature. If cells are put in when they are either too mature or immature they cannot make the new connections required to restore vision. The equivalent stage in human development occurs during the second trimester of development in the womb and so makes finding a direct source of precursor cells very unlikely. However, it does mean that scientists now know what they need to do to stem cells in order to get a transplantable source of donor cells – they need to make ‘baby’ photoreceptors in the laboratory. This has been achieved very recently at UCL Institute of Ophthalmology using mouse embryonic stem cells that were grown in a 3D culture system to form immature retina. By using markers to specifically identify the photoreceptor precursors, the researchers were able to take the precursor cells and transplant them into mouse models of RP.