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At the Nexus of Eye Research

Scientists and ophthalmologists in Australia, the UK and Canada are pushing the limits of corneal regeneration

Researchers in Australia have developed a method to amplify endothelial cells in the lab, potentially transforming corneal transplant procedures and addressing the global shortage of donor corneas. Meanwhile, collaborative efforts in the UK and Canada are exploring collagen-based artificial corneas, offering insights into corneal regeneration.

A revolutionary technique developed by Australian scientists could allow a single cornea donation to facilitate multiple transplants, significantly expanding the pool of available tissue. This development not only addresses the critical shortage of corneal donors but also offers new hope to millions affected by corneal blindness.

Across the globe, researchers at Cardiff University and Montreal University are exploring the potential of collagen-based artificial corneas, aiming to improve healing and understanding of corneal structures. This breakthrough research may open new avenues for treating corneal disease and enhancing regenerative medicine.

From lab to life: Hope in tackling donor shortage

Researchers in Australia have found a way to amplify endothelial cells in the laboratory that will help solve the global shortage of cornea donors. The development means around 50 transplants could be possible from a single cornea donation, offering hope to cure blindness in many more patients than is currently possible.

It is a potential ‘game changer’ in corneal transplants, which could see 40 to 50 transplants from a single donation, shared Prof. Mark Daniell, head of corneal research at the Centre for Eye Research Australia in Melbourne, Australia.

Prof. Daniell, who is also a senior consultant at the Royal Victorian Eye and Ear Hospital in Melbourne, initiated the study more than a decade ago with researchers at the hospital. They first discovered that endothelial cells could be grown in the laboratory, something they do not do in the human body.

Prof. Daniell then met with engineers from the University of Melbourne, who developed folding ‘scaffolding’ on which the cells could be grown before being inserted into the eye. Made from the same substance as edible capsules, it pops open once inside the eye, said Prof. Daniell, and is completely biodegradable, dissolving without causing any inflammation.

“With this scaffold, we now have a method for culturing the cells outside the body, expanding the pool of donors, and introducing them into the eye,” explained Prof. Daniell. “It’s a type of surgery that you don’t need to be a super expert in corneal surgery to do,” he added. “You just need to be able to do the usual corneal surgical techniques.

So far, the research has been tested in multiple sheep and is going through regulatory approval for human trials.

The future of tissue engineering

According to Prof. Daniell, the impact on patients could be immense, with around 12 million people blind from corneal disease worldwide and only 100,000 transplants performed currently each year.

He added that the greater availability of transplant tissue should particularly impact developing countries, where a lack of infrastructure creates a severe shortage of access to donated corneas.

A company called BIENCO was established through collaboration among the Centre for Eye Research Australia, the University of Melbourne, the University of Sydney, the University of Wollongong and Queensland University of Technology. Bienco will focus on developing complete corneas.

“The idea is that we will have the capability to replace any part of the cornea that we want, and we can do that at the order of the surgeon,” shared Prof. Daniell.

Prof. Daniell is also working on further research that could completely eradicate the need for donors by using a person’s own tissue from another part of the body to grow endothelial cells.

“Theoretically, we’ve now done it in the lab: You can take skin cells and induce them to become pluripotent stem cells. Once they’re induced, those stem cells can keep growing forever. You can then convert them back into corneal cells,” he explained.

Researchers are now at the stage of trying to prove that the grown cells function like normal corneal endothelial cells, he added.

“That holds great promise because it allows us to take some cells from a pinch of someone’s skin, and after some time in the lab, turn it back into a cornea. It could be possible to grow a cornea from just a bit of skin or some other basic tissue,” he said.

New avenues in Regenerative Cell Research

Researchers at Cardiff University in the United Kingdom have been studying the ability of collagen cornea implants to activate healing in damaged eyes.

The research offers not just a promising development in curing blindness for many, but also a greater insight into the cornea that could aid further research.

“We aim to better understand the structure of the cornea and how diseases affect vision,” said Dr. Phil Lewis, a structural biophysics fellow at Cardiff University, who is involved in the research project.

The Cardiff team’s research is in collaboration with a group at Montreal University in Canada, led by Dr. May Griffiths, a professor in the Department of Ophthalmology. In 2010, her group developed an artificial cornea, tested in around 10 patients, which was made of labgrown recombinant collagen type 3, similar to the collagen that makes up the majority of the eye.

Those corneas, placed into the eye as a scaffolding structure, were intended to mimic the collagen in the cornea. It was found to encourage keratocytes, repair cells within the body and lay down new human collagen—gradually replacing the introduced structure and repairing the eye.

Dr. Griffith’s group has since developed artificial versions of this collagen structure called synthetic peptides, which are cheaper and faster to produce than the original natural lab-grown material. She has also shifted from hard structures to ‘liquid corneas,’ said Dr. Lewis, which are like a gel that can be injected into a small wound.

Other agents, such as antiinflammatories, have been added to the artificial corneas, and it is important to understand their impact, added Dr. Lewis.

The Cardiff team hopes to understand how the collagen structures work, why they encourage regeneration and what is best in terms of biocompatibility and speed of repair.

“We are looking at what’s happening during regeneration,” said Dr. Lewis. “We don’t want to create something new that doesn’t work, such as cornea with hazing,” he added.

As well as assessing the effectiveness of Dr. Griffith’s work mdaniell@cera.org.au and understanding how her artificial corneal structures function, the Cardiff team’s research also provides a better understanding of the cornea in general. This could open up new research areas, such as studies of regenerative tissue in other parts of the body—concluded Dr. Lewis.

Editor’s Note: A version of this article was first published in CAKE Magazine Issue 24.

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Dr. Philip Lewis, BSc, MSc, PhD

Dr. Philip Lewis, BSc, MSc, PhD, is a research fellow in the School of Optometry and Vision Science, Structural Biophysics Group, at Cardiff University. He has been part of the group for the last 20 years. His work has primarily been focused on the structural biology of the cornea in health and disease, the structural basis of corneal development in human and animal models, and the development of artificial corneas. He is also the group’s electron microscopist specializing in Cryo Transmission Electron Microscopy and the 3D Volume scanning technique of serial block face electron microscopy.

[Email: LewisPN@cardiff.ac.uk]

Prof.Mark Daniell

Prof. Mark Daniell

Prof. Mark Daniell is a senior consultant ophthalmic surgeon with a distinguished career in ophthalmic practice. He is head of the corneal service at the Royal Victorian Eye and Ear Hospital (RVEEH), overseeing a team of surgeons performing corneal transplantation. He is founding chair of the ANZ Corneal Society and medical director of the Lions Eye Bank. Previously he was head of ophthalmology at the Royal Melbourne Hospital. Prof. Daniell is also leader of the Hygelix consortium and comedical director of BIENCO, a national collaboration developing a bioengineered cornea, funded by the Medical Research Future Fund. In addition, he is head of surgical research at the Centre for Eye Research Australia and founder of the Keratoconus International Consortium. He was previously chairman of the Ophthalmic Research Institute of Australia (ORIA) for six years and continues to review grants for the National Health and Medical Research Council and ORIA. He has served on the RANZCO board for 10 years and is the organization’s immediate past president. Prof. Daniell has achieved over $40m in competitive grant funding from MRFF, VMRAF, AISRF, ORIA, NHMRC, and University of Melbourne interdisciplinary grants. He is the current beneficiary of the Frontiers of Health MRFF grants for tissue-engineered cornea projects. He has published 142 papers in peer-reviewed literature and has an H-index of 38.

[Email: mdaniell@cera.org.au]

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