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Lab-grown corneas could prevent blindness

“Scientists regrow corneas in breakthrough that could pave the way for a cure for blindness,” reports the Mail Online.

Researchers in the US have found a way to identify the stem cells that renew the cornea (the clear layer that covers the front of the eye), and have used them to grow normal corneas in mice.

These stem cells – called limbal stem cells (LSCs) – are known to be the basis of cornea renewal, but there has not been a way to harvest them before now.

Through a number of laboratory experiments, the researchers found that a protein called Abcb5 is located on the surface of the LSCs.

The protein can now be used as a marker to identify and separate them from other cells.

They also showed that transplanting the isolated human LSCs into mice lacking these cells caused them to develop normal corneas after five weeks, and then maintain them for over a year.

The hope now is that these cells could be used in human corneal transplants to enriched them with lots of these LSCs to improve the chances of success. However, this would depend on the condition being treated, with the long-term success rate of corneal transplants ranging between 60% and 90%.

Additional research is likely to be needed to refine and further test the technique before it can be tested on humans.

Where did the story come from?

The study was carried out by researchers from Harvard Medical School, Boston Children’s Hospital, Brigham and Women’s Hospital, and several other US Universities. It was funded by the National Institutes of Health, a Harvard Stem Cell Institute grant, the Department of Defense, the Corley Research Foundation and the Western Pennsylvania Medical Eye Bank Core Grant for Vision Research.

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

The UK media have accurately reported this story.

What kind of research was this?

The research comprised a series of laboratory and animal experiments, which aimed to analyse stem cells in the cornea to help improve the success rates of corneal transplants.

The cornea is the clear, outer layer that covers the front of the eye and, like a lens, helps focus light onto the retina. It is constantly renewed by LSCs, which are located in one layer of the cornea.

A number of conditions can result in a reduced number of LSCs, which prevents the cornea from repairing itself adequately.

This means that it can become opaque (stop being clear), causing reduced vision and blindness.

LSC deficiency can be due to congenital conditions and from injury due to radiotherapy, chemical burns, contact lens wear and inflammatory conditions.

Management of LSC deficiency includes maintaining a healthy surface of the eye with artificial tears and, if necessary, topical steroids. If surgery is needed, a transplant of healthy cornea from a donor (usually deceased) can be used. Studies have shown that the number of LSCs within grafts is critical for long-term transplant success. However, there is currently no easy way to select these cells from other corneal cells. This research investigated whether they could develop a technique to identify and separate out LSCs, with a view to being able to increase their number and thus improve success rates.

What did the research involve?

The researchers conducted several experiments using human corneal samples, staining and imaging techniques, and mice to find a way of identifying functioning LSCs.

They first investigated whether a protein that is present on the surface of other types of skin stem cells, called Abcb5, is also present on LSCs. They then looked at whether the presence of this protein identified LSCs specifically by examining whether the presence of the protein predicts a cell’s active properties in cell renewal.

To test whether the presence of the Abcb5 protein on the LSC is necessary for corneal repair, the researchers compared mice genetically modified to lack a key part of this protein (knockout mice) and normal mice.

The knockout mice were able to see, but had thinner corneas, and the corneal cells had a disorganised pattern.

The researchers compared their wound healing abilities by making an injury to the mice’s cornea, and measured how quickly and effectively the wounds healed.

This was done to see if the lack of protein affected how well the LSCs could generate new cells to repair the cornea.

They also transplanted mouse and human LSCs with and without the Abcb5 protein into mice and monitored the regrowth of the corneas. They looked at long-term (more than one year) results from this corneal restoration.

This was done by putting the LSCs into a fibrin based gel, removing the corneal and limbal epithelium of anaesthetised LSC-deficient mice and transplanting the LSC-containing fibrin gel, and suturing it in place.

What were the basic results?

The Abcb5 protein was present on the surface of the LSCs and seemed to specifically identify these cells rather than other cells in the cornea. Using antibodies to the Abcb5 protein allowed researchers to separate out the LSCs from other cells without damaging them.

The cornea of normal mice and knockout mice without the Abcb5 protein healed at the same rate. However, the repaired cornea in the Abcb5 knockout mice showed irregular and fewer corneal cells, compared to the normal mice.

The mice with an LSC deficiency were given either mouse or human corneal grafts. There were three basic results. The mice that had:

  • LSCs without Abcb5 developed abnormal corneas.
  • A mixture of LSCs with and without Abcb5 had partial corneal restoration.
  • LSCs with Abcb5 developed normal, clear corneas. 

How did the researchers interpret the results?

The researchers concluded that “the identification and prospective isolation of molecularly defined LSCs with essential functions in corneal development and repair has important implications for the treatment of corneal disease, particularly corneal blindness due to LSC deficiency”.

Conclusion

This study has identified that the cell surface protein Abcb5 is necessary for normal function of LSCs in renewing the cornea. It has also shown that LSCs can be separated out from other cells through the use of antibodies to the Abcb5 protein without causing damage to the LSCs. This means that it should be possible to gather these cells (in preference to other cells) and use them to provide the best chance for a successful corneal transplant.

It is important to note that the mice were given genetically identical grafts or completely immunosuppressed so that they did not reject the grafts. At present, human recipients of donor corneal transplants also have to have immunosuppression to try to prevent the body from rejecting the transplant, unless the corneal transplant was from their good eye (but this can lead to a risk of LSC deficiency in this donor eye). Rejection is a common problem that currently affects around one in five transplant cases.

Immunosuppression and possible rejection would still be a consideration in using this new technique.

Though there is a possibility that researchers may be able to find a way to harvest normal LSCs from the person requiring the transplant and multiply them in the laboratory, before transplanting them back.

Though this research provides a new approach to capturing important cells for corneal regeneration, more research to develop the technique and make sure it is safe will be required before human trials can take place.

As is the case with all donated organs, the current demand for transplanted corneas outstrips the demand, so if you haven’t already signed up to the organ donation register, please do so.

Adding your name to the Organ Donor Register will only take a few minutes.

That way, you can be sure that your corneas and other valuable organs don’t go to waste after you die.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

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