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Stem Cells in Focus

Stem Cells May Be Key to Curing Retinal Disease

By Maya Chaddah | May 9, 2014
Expert Contributor: Robin Ali, PhD

In recognition of Healthy Vision Month, the ISSCR is highlighting the exciting advancements related to stem cell research and vision repair.

A team of UK stem cell scientists, led by Dr. Robin Ali from UCL Institute of Ophthalmology in London, has developed a new strategy for repairing the retina by transplanting photoreceptor cells generated in the laboratory from embryonic stem cells. There is a good precedent for using stem cell therapy to repair eye damage. Transplanting corneal stem cells to repair chemical burns of the cornea has been very successful in restoring vision. But the retina – a multi-layered neural network – is a much more complicated structure, so repairing it poses greater challenges.

Stem Cells in Focus Webcast

Treating Vision Loss With Stem Cells

Robin Ali, PhD, Institute for Ophthalmology, University College London, UK

Learn more about the research and its potential, and pose your questions directly to Prof. Ali, during a live public webcastThursday, May 15 at 2 pm ET (USA).

The retina is a thin tissue at the back of the eye. It contains millions of neurons, including photoreceptors that are the light-sensing cells of the retina. Other neurons process and relay light information from one layer to the next. The relay ends at ganglion cells. These neurons communicate via the optic nerve to the brain, which assembles information from the retina into visual pictures. The outermost layer of the retina - called the retinal pigmented epithelium or RPE for short –supports the other layers. 

Dr. Ali explains that researchers are looking at several different stem cell strategies for repairing the retina. One strategy is to repair the RPE layer, which is damaged during progression of diseases such as age-related macular degeneration (AMD) and Stargardt disease. A second strategy is to replace the photoreceptors that are lost in diseases such as retinitis pigmentosa, AMD and diabetic retinopathy. Loss of photoreceptor cells is the most common cause of blindness in the developed world. Since damage to the RPE layer leads to death of the neighboring photoreceptors, in many cases it might be necessary to use a combined approach to repair both the RPE and photoreceptor layers. Another strategy involves the replacement of retinal ganglion cells that are lost in diseases such as glaucoma.

Various types of stem cells are being explored for the purpose of transplantation but to date embryonic stem cells –cells that can make any cell type in the body – are best suited for making retinal cells for transplantation.

Compared with other parts of the body, the eye is a very amenable organ for assessing stem cells therapies:

  • the eye is very accessible, so it is easy to deliver treatments very precisely and to monitor the outcomes;
  • there is a natural interface between the photoreceptor and RPE layers, so cells can be injected between these layers and have good access to either;
  • immune responses are dampened down compared with most other parts of the body, and this might help for avoiding transplant rejection;
  • since we have two eyes, one can be treated and other left untreated to evaluate if interventions have any effect.

Methods to repair damaged RPE with RPE cells generated from embryonic stem cells have reached the first, small-scale human clinical trials. It is not yet known whether the transplants will be tolerated long-term, but the safety profile appears promising and larger trials are underway.

Research around how to repair the photoreceptor and ganglion layers is still at the pre-clinical stage. This is a much trickier task for two reasons: it is harder to grow neurons from embryonic stem cells; and to be useful, the transplanted photoreceptor and retinal ganglion cells need to integrate and make functional connections with existing neurons. Dr. Ali thinks that learning how to replace ganglion cells could take a very long time because the cells have to make very long connections along the optic nerve to the appropriate parts of the brain. But photoreceptors only need to make short connections with the adjacent layers of neurons. 

Dr. Ali’s team has previously shown that transplanted immature rod photoreceptor precursors taken from the retinas of neonatal mice can make the necessary connections within the retina to restore the night vision of adult mice that could not see in dim light before treatment. In testing their therapy, they examined the visual cortex of mice that had received transplants and showed that a visual stimulus to the treated eye triggered brain activity. They also performed behavioral tests to confirm that the mice could track dim light and cognitive tests to demonstrate that they could swim towards dim light.

Dr. Ali has now discovered a way to generate and purify from embryonic stem cells, enough photoreceptors at just the right stage of development for effective transplantation. The technique, first developed by Japanese researchers and adapted by Dr Ali’s team, involves generating from embryonic stem cells balls of cells called embryoid bodies, which under the right growing conditions, will self-organize into little budding organs called optic cups. Rod photoreceptor precursors at just the right stage for transplantation can be extracted from these optic cups and transplanted into adult mice with degenerated retinas.

The next steps will be to find ways to transplant cone photoreceptors more efficiently. These cells work in daylight and are responsible for our central vision, allowing us to detect color and see fine details. In the future it will also be important to optimize the transplant method in mouse retinas that have more damage and scarring. The ultimate goal is to apply what has been learned from the mouse studies to humans and to find ways of developing clinical grade production of human embryonic stem cell-derived photoreceptors for transplantation.

Dr. Ali and his team look forward to the day – perhaps 5 years down the road – when they will take their embryonic stem cell research into meaningful clinical trials that will inform how they move safely forward with a stem cell therapy for retinal disease. 

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