Scientists grow eye structure in lab

Scientists have grown an “embryonic eye”, according to The Daily Telegraph. The newspaper says that this brings eye transplants to cure blindness a step closer.

The researchers have grown a structure similar to the retina – the light-sensitive layer at the back of the eye which allows us to see – from mouse embryonic stem cells. The embryonic retina-like structure included both a layer of pigment-containing cells, and a layer of nerve cells, making it similar to the normal retina. While having a structure similar to a normal retina, further research will be needed to determine whether these structures function in a similar way, whether these cells can successfully be transplanted and whether they enhance sight once in the eye. These experiments will need to be carried out in animals before anything similar could be considered in humans.

Even if these laboratory-grown retinas eventually prove unsuitable for transplants, they should help scientists to better understand how the retina develops and how it is affected by disease. They may also be useful for testing the effects of various drugs on the retina in the laboratory. Overall, this appears to be an important step forward for retinal research.

Where did the story come from?

The study was carried out by researchers from the RIKEN Center for Developmental Biology and other research centres in Japan. It was funded by MEXT, the Knowledge Cluster Initiative at Kobe, the S-Innovation Project and the Leading Project for Realization of Regenerative Medicine.

The study was published in the peer-reviewed scientific journal, Nature.

The Daily Telegraph, BBC News, the Daily Mail, and The Guardian have covered this story. The Telegraph suggests that the “the cells were functioning normally and were capable of communicating with each other”. Although the cells were able to organise themselves into three-dimensional, retina-like structures successfully, the researchers have not yet looked at whether the cells in these structures can sense light or transmit nerve impulses to the brain.

The Daily Mail provides an illustration of how retinal cell transplants could potentially work. It says that people with a particular form of sight loss called age-related macular degeneration (caused by degeneration of the light-sensitive cells in the retina) could benefit “within years”. However, much more research is needed before we will know whether such transplants might work, and they are not guaranteed to be feasible.

What kind of research was this?

This study aimed to see whether mouse embryonic stem cells could be induced to form a structure similar to the developing retina in a laboratory setting.

The retina is the light-sensitive layer at the back of the eye, which allows us to see. In embryonic development, the cells that eventually form the retina initially form what is called the optical vesicle, which then forms a two-walled cup-like structure called the optic cup. This then develops into the outer layer of the retina, which includes the pigmented cells and the inner layer of the retina, which contains the light-sensitive nerves that are involved in transmitting information from the eye to the brain. This process of development is complex, and is influenced by the neighbouring tissues. The researchers wanted to see if they could copy this process in a laboratory in the absence of these neighbouring tissues.

What did the research involve?

The researchers had previously been able to get mouse embryonic stem cells to develop into retinal-like cells, but had not been able to get these to develop into the layers of cells seen in a normal retina. In this study, they improved this process by including molecules that would normally be found in the environment of the developing eye, as well as a protein which forms a gel to support the cells.

They then observed what happened when mouse embryonic cells were grown in these conditions. They looked at whether the cells would form three-dimensional structures, and what type of cells they resembled, based on which genes they switched on. They also took videos of the developing cells using special microscopes, and carried out further studies to look at which proteins were important in this developmental process.

What were the basic results?

The researchers found that their modifications to their original techniques lead to more of the mouse embryonic stem cells developing into retinal-like cells. They also found that these cells began to align themselves into hemispherical structures. The front portion then folded in to form a structure that resembled an optic cup.

This optic cup structure then formed into a layered structure resembling a normal retina. The inner layer of cells switched on genes typical of the nerve cells of the retina, and the outer layer switched on genes typical of the pigmented cells of the retina. No lens-like structure was formed.

The retina-like structures could be grown in the lab for up to 35 days, after which they gradually degenerated.

How did the researchers interpret the results?

The researchers concluded that it is possible to replicate the complex formation of three-dimensional embryonic retina tissue structures in the laboratory, and that this process could be achieved without the need for neighbouring tissues. They say that this “heralds the next-generation of generative medicine in retinal degeneration therapeutics, and opens up new avenues for the transplantation of artificial retinal tissue sheets, rather than simple cell grafting”.

Conclusion

This complex research has illustrated that retina-like structures, with similar three-dimensional structures and cell types to the normal retina, can be grown in the lab from mouse embryonic stem cells. This process may not be identical to what happens in the developing body, where neighbouring tissues influence the process. It is hoped that if a similar process could be achieved with human cells, these could be used to treat retinal problems. However, a lot more research will be needed before this could become a reality.

This research did not test whether the cells and structures produced were able to translate light into nerve signals, so the researchers will next need to look at whether these lab-grown retinas can perform the sensory functions of a natural retina. If the cells do appear to function appropriately, they would then need to determine whether these cells could be successfully transplanted into the eye, and whether they can function properly, integrate with existing eye structures, and enhance sight once in the eye. These experiments will need to be carried out in animals, before anything similar could be considered in humans.

However, even if these laboratory-grown retinas are not eventually usable in transplants, the ability to grow retina-like structures in the laboratory should help scientists to understand more about how the retina develops and how it is affected by disease. They may also be useful for testing the effects of various drugs on the retina in the laboratory. Overall, this appears to be an important step forward for retinal research.