New cell regeneration technology helps restore eyesight

08 Jun 2017

Author: John Pickrell

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A University of Melbourne team has developed a way to grow corneal cells in the lab that may eliminate the need for donor corneas and restore eyesight to millions of people worldwide.
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Corneal disease is a debilitating eye condition that leads to blindness and currently affects 10 million people worldwide. The only solution currently available is a cornea transplant.

But a new treatment developed by researchers at the University of Melbourne and the Centre for Eye Research Australia (CERA) might one day eliminate the need for donor corneas and reduce the risk of post-transplant rejection. 

Dr Berkay Ozcelik has developed the world’s first fully synthetic hydrogel film. Transparent and thinner than a human hair, the film can naturally regenerate corneal endothelial cells on its surface. It is implanted via a minute incision in the cornea and dissolves in two months, leaving the new cells behind.

Ozcelik and his co-workers have grown cells on film and successfully implanted them into the eyes of sheep to restore vision. With luck and sufficient funding, they hope to begin human trials in 2018–19, which could lead to the treatment being publicly available by 2022. 

“Looking down the microscope and seeing these cells growing on the film for the first time just blew me away,” Ozcelik says. “It was a very rewarding feeling to actually be able to achieve that.

“What really drives me is the potential to help millions of people worldwide and give them a much better quality of life.”

Growing corneal cells in the lab

The cornea is a very thin, transparent layer at the front of the eye. To stay functional and transparent, it must remain thin – special cells known as corneal endothelial cells aid this by pumping water out of the cornea. But injury, ageing and disease can reduce the number of these cells, causing the cornea to thicken and lose its transparency, eventually leading to blindness.  

Corneal transplantation is fraught with difficulties. “It’s difficult to transplant corneas back into patients as the cell layer is very fragile,” says Ozcelik. 

A patient’s immune system is also primed to recognise and reject this foreign tissue, which means they must take immune-suppressant drugs such as steroids for the rest of their lives.  

“About a third of corneal transplants suffer from rejection and have to be replaced,” says Associate Professor Mark Daniell, an ophthalmic surgeon at CERA. 

Getting donor corneas is also a big problem in much of the world, particularly China, Japan, Russia and India. In China and Japan in particular, there is a cultural aversion to donating corneas, meaning that hundreds of thousands of people remain blind unnecessarily. 

A tissue-engineered cornea would overcome the twin problems of a lack of donors and the rejection of corneas. Daniell had been part of a team growing corneal cells in the lab, but he needed a synthetic scaffold that would be implantable in the eye. He approached Greg Qiao, a professor of macromolecular chemistry and engineering at the University of Melbourne, and his then PhD student Ozcelik.

“Berkay developed a whole lot of potential substrates to grow the cells on and to use as a scaffold,” Daniell says. “He came up with this final formulation which is incredibly useful for us. We have something the cells like to grow on and that we can use during the surgery.”  

Procedure from University of Melbourne

Saving the eyesight of millions

Ozcelik says his team has an ultimate goal beyond simply improving the success rate of transplants: “We have two objectives with this work: we want to eliminate the need for donor tissue and we want to minimise shortages of donor material.” 

Firstly – if there are enough viable corneal endothelial cells left in a patient’s own eye – they aim to remove and culture them in the lab for transplantation back into the eye. If this succeeds, it could remove the problem of rejection and reduce the need for donor corneas. 

However, some patients may not have enough viable corneal cells prior to treatment. In that case, they will still need donor cells, but if researchers can culture them in the lab and grow them on films then a single donor cornea can go a long way.

“Currently you transplant one cornea from one donor to one patient,” says Ozcelik. “However, with the ability to culture these cells on the synthetic film we can increase the use of donor material. So instead of one donor to one patient, we might be able to do one donor to 20 patients.”  

Another benefit of the film is that it is significantly more robust than the natural tissue. “We’ve had cases of surgeons having to spend four hours opening up the donor film, as it tends to curl up,” says Ozcelik. In contrast, his synthetic ‘hydrogel’ soaks up water and expands, preventing it from curling and reducing handling. 

Looking to the future, Ozcelik says that the same kinds of films could be used to grow other types of cell in the laboratory, such as skin cells for transplant. 

Collaboration the key to success 

Berkay Ozcelik 

 Ozcelik, the son of Turkish emigrants to Australia, was a fiercely curious child. His interest in tissue engineering research began at high school when he heard tales on the news about the success of stem cell treatments and the potential for regenerating human tissues.

“Luckily for me I was able to follow that interest through to studying biomedical engineering at the University of Melbourne, and then doing my PhD there on tissue regeneration,” he says.

Ozcelik has won several awards for his work, including being the Victorian winner of the Fresh Science national competition for early-career researchers and the Australian national science agency CSIRO’s John Philip Award for Excellence 2016 for his work on antimicrobial coatings.

“What I am trying to do is work across many fields to improve the quality of life for millions of people around the world,” he says. “Collaborating and working together with researchers from across the globe is ultimately how we will achieve success.”