Genetics and stem cells

Donated human eye cells could help restore vision

"Cells from eyes of dead 'may give sight to blind'," BBC News reports. This gruesome sounding news is based on a study that found that after being grown in the lab, a type of cell found in the retina could restore limited vision in rats. However, the research was carried out in rats genetically engineered to develop visual impairment, so it's not something that will be used to treat people any time soon.

The cells in question are called human Müller glia with stem cell characteristics (hMSCs). hMSCs have the potential to develop into another type of specialised visual cell known as rod cells. Rod cells are sensitive to changes in light, shape and movement, so are essential for vision.

Rod cells made from donated adult human retinas offer the possibility of stem cell therapies for retinal diseases such as age-related macular degeneration. Currently, it is only possible to transplant corneas (the outer part of the eye) in humans.

But, as with all transplant therapy, there is the possibility that the body could "reject" the transplant. It may be possible for hMSCs to be taken from the visually impaired person directly, avoiding the need for a donor. This approach has been successfully used in bone marrow transplants.

Studies in people are now needed to see whether this would be an effective approach for treating retinal diseases.

Where did the story come from?

The study was carried out by researchers from the University College London Institute of Ophthalmology and Moorfields Eye Hospital NHS Foundation Trust.

It was funded by the Medical Research Council, the Royal College of Surgeons of Edinburgh, the National Institute of Health Research, and Fight for Sight, a charity that funds research into blindness and eye disease.

The study was published in the peer-reviewed journal, Stem Cells Translational Medicine.

The research was covered well by BBC News, which explained some of the potential pitfalls of using transplanted cells, such as the possibility of rejection.

The reporting also included useful insights from the researchers on what the increase in rod cell function would allow people to do, such as being able to detect objects but not being able to read words.

What kind of research was this?

This was a laboratory and animal study. The researchers aimed to develop a protocol that would cause hMSCs to develop into rod photoreceptors in the laboratory.

These cells act as support cells for the neurons (nerve cells) found in the retina, the light-sensitive tissue that lines the inner surface of the eye. Previous research found that hMSCs can develop into different types of eye cell under certain conditions.

Rod photoreceptors are one of two types of cell in the retina that respond to light, the other being cone cells. Rod cells are most sensitive to light and dark changes, shape and movement, and only contain one type of light-sensitive pigment. They are not good for colour vision.

The researchers then looked at whether the human rod photoreceptors they had developed could function as rod cells in a living animal. They tested this by transplanting the cells into rats that had been genetically modified to have primary rod photoreceptor degeneration. They looked at whether the transplanted cells could restore the response of the rats' eyes to light.

What did the research involve?

The researchers isolated hMSCs from donated human retinas. They grew the cells in the laboratory under specific conditions previously shown to cause embryonic stem cells and induced pluripotent stems cells to develop (differentiate) into rod cells. The researchers checked that their differentiated cells made the key genes and proteins that rod cells make.

They then transplanted the cells into the retinas of rats that had been genetically engineered to have rapid primary photoreceptor degeneration, where the light-sensitive cells that make up the retina die out.

The researchers looked at where the cells were located after transplantation, and then looked at whether the transplanted cells could improve rod function in the rats. They did this using a technique called flash electroretinography – which measures the electrical response of rod cells in the retina – four weeks after transplantation.

What were the basic results?

The researchers found that when the hMSCs were grown under specific conditions, they changed shape and made the genes and proteins that rod cells make.

When these cells were transplanted into the rats' retinas, they integrated into the retina and expressed photoreceptor and synaptic markers close to the site of transplantation. This means that they produced the same sort of biological markers you would expect to see in rod cells.

Rats that had been transplanted with the cells had a significant increase in rod photoreceptor function four weeks after transplantation.

How did the researchers interpret the results?

The researchers concluded that, "This study has demonstrated that hMSCs isolated from the normal adult human retina may be cultured in the laboratory to generate a source of rod photoreceptor precursors suitable for transplantation.

"Such cells may also offer the potential of developing autologous therapies [where the cells are taken from the person, rather than a donor] for human application.

"On transplantation into the subretinal space of a rodent model of primary photoreceptor degeneration, these cells migrated and integrated into the retina, and caused significant improvement in photoreceptor function in vivo. hMSCs may therefore be regarded as an alternative source of cells for the development of future therapeutic strategies to treat photoreceptor disease."

Conclusion

This study has found that rod cells developed from hMSCs in the laboratory could restore rod cell function in rats that had been genetically engineered so that their rod cells died.

This offers the potential for treatment that could restore the vision of people with visual impairment of the broad perception of light and dark, the size and shape of objects, and movement. Even though restoring some rod cell function would not provide detailed vision, it could help with carrying out normal activities of daily life, such as moving around and getting food and drink.

As the researchers say, using rod cells derived from cells in the adult human retina would be free from some of the ethical concerns regarding the use of embryonic stem cells (very early stage stem cells that can be developed into any cell in the human body). This technique could also be cheaper and simpler than obtaining induced pluripotent stem cells (stem cells generated from adult cells).

While using donor cells from another person could mean there is a possibility that the body could "reject" the transplant, the researchers suggest that it could be possible for hMSCs to be taken from the person themselves, avoiding the need for a donor. Further research in people is needed to see whether this would be an effective approach for treating retinal diseases.

Currently, many eye conditions cannot be successfully cured, although there are treatments that can be used to prevent symptoms from worsening and help preserve vision.

This is why it is important to have regular eye tests. It's recommended that adults have their eyes tested every two years, although people with a history of sight problems may require more frequent tests. 


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