January 2016

 

NEWS & OPINION

 

New AMD vision coming to fruition


by Maxine Lipner EyeWorld Senior Contributing Writer

 
   
molecule COCO

With the aid of a molecule called COCO, normally found in the developing retina, human embryonic stem cells were grown into cone photoreceptor sheets such as this one.

retinal sheetsInvestigators hope to see whether retinal sheets like this, made from human embryonic stem cell cells, can be transplanted into rabbits.

Source: Gilbert Bernier, PhD

Using stem cells to restore sight

For those with age-related macular degeneration (AMD), the promise of stem cell therapy that enables transplantation of photoreceptors may be closer than ever. A new technique that allows for the abundant production of cone photoreceptors is being developed, according to Gilbert Bernier, PhD, associate professor, Department of Neuroscience and Ophthalmology, University of Montreal. We developed a protocol using one very efficient molecule, which allowed the differentiation of 80% of stem cells into cone photoreceptors in the dish, he said. That is unprecedented. In AMD, the degeneration of the macula is caused by the destruction of the cones and cells in the retinal pigment epithelium. When attempting to treat this, the problem is that the human retina is quite big, requiring an abundant source of cells for replacement therapy, Dr. Bernier said. The human macula contains between 4 and 5 million cells, which are all cone photoreceptors, he said, adding that because human embryonic stem cells can be expanded without limits, these are potentially the best source for transplantation. These can generate any cell type of the human body and can, in principle, even create a human embryo, he said.

Generating cone receptors

However, the challenge has been to direct the differentiation of these stem cells, which could potentially be made into thousands of different cell types, Dr. Bernier noted. You need to understand how an individual cell type is controlled during normal development to push them toward a single cell type, he said. While other techniques have been tried, the issue has been a low yield of embryonic stem cells transforming into cones. People could get 4, 5, or at best 10% of cone photoreceptors from embryonic stem cells, Dr. Bernier said. The [previous] protocol had been generated by a Japanese group, and it took them 6 months to end their protocol of differentiation. Of the cells produced by the Japanese protocol, only about 10% became cones. If you want to do cell transplantation when 90% of your cells are contaminated, you have a big problem, Dr. Bernier said, adding that the cells must be purified, and with a need for 4 or 5 million, such a limited yield will not work.

By contrast, with their technique, 80% of cells converted into cones within 1 month, Dr. Bernier reported. Whats more, these were more than just cells in a dish; they were stacks of photoreceptors very close to being ready for transplantation, he said, adding that it was nearly a human macula.

As part of the technique, investigators used human embryonic stem cells and grew these toward confluence. Then, just before they would normally differentiate, they added a molecule known as COCO that they found existed during normal development. Its normally expressed in the developing retina and in adults its highly expressed by photoreceptors, Dr. Bernier said. As part of this process, the human embryonic stem cells were placed directly in a flat dish, and these, with the aid of COCO, grew into retinal sheets.

Clinical horizon

The goal from a clinical perspective is to produce more than just individual cells. The whole idea is we could go ahead with this approach and graft the tissue to replace the diseased macula, he said, adding that in AMD and Stargardt cases, not only are the photoreceptors sick and dying, but the retinal pigment epithelium is sick as well. With the new process, the group has been working on tissue reconstruction, generating a pure monolayer of retinal pigment cells, as well as stacks of photoreceptors or retinal sheets. Once this is completed, we take the retinal sheet and put it on the retinal pigment cells and let them grow together, Dr. Bernier said. This bioengineered tissue, which contains a monolayer of RP cells with a stack of photoreceptor cells on top, is what will be transplanted, he said.

Associated cells have been transplanted into mice, and it has been shown that these can integrate into the mouse retina. Now investigators want to see if retinal sheets produced from human embryonic stem cells with the technique can be transplanted by retinal surgeons into rabbits, which have larger eyes, Dr. Bernier noted. By January 2016, were going to graft that, he said. However, there is no telling what the timeline may be in humans. While the science is available, the paperwork may take years, Dr. Bernier said. One of the limiting factors for his group at present is money, which is in short supply. More funding could make a significant difference for implementation.

Editors note: Dr. Bernier has no financial interests related to this article.

Contact information

Bernier
: Bernierg2@gmail.com

New AMD vision coming to fruition New AMD vision coming to fruition
Ophthalmology News - EyeWorld Magazine
283 110
220 81
,
2017-04-23T12:01:08Z
True, 1