New research led by scientists at Newcastle University, UK reveals a potential revolutionary way to treat eye injuries and prevent blindness – by softening the tissue hosting the stem cells which then helps repair wounds, inside the body.
The team discovered that the simple application of a tissue-softening enzyme, collagenase, prevents the loss of corneal stem cells following an injury and could prevent patients from losing their sight. It offers hope to almost 500,000 people a year who lose their sight due to chemical burns including acid attacks.
The study, published in Nature Communications and funded by the Medical Research Council shows that keeping corneal stem cells in a soft environment is fundamental for their reproduction, self-renewal, and ability to heal damaged tissue.
This discovery was made possible by the development of a sophisticated microscopy technique which enables imaging the physical properties of biological tissues at very high resolutions. Using this technology in collaboration with experts in Photonics from Imperial College London, the team was able to determine that the corneal stem cell niche – the area of tissue in the cornea where stem cells live – is a much softer environment than the rest of the tissue.
The scientists also discovered that stiffening the niche causes stem cells to mature and lose their self-renewing and wound healing properties.
Dr Ricardo Gouveia, Research Fellow at Newcastle University and first author of the paper said: “This study demonstrates a potential new way to treat injuries by changing the stiffness of the natural environment which we have shown changes the behaviour of the adult stem cells. Our imaging approach provides a valuable tool to analyse live cells within the cornea, as well as to further explore new therapies for restoring or even improving their function.”
As the outermost layer of the human eye, the cornea has an important role in focusing vision yet many of the processes keeping it transparent and resistant to damage are not well understood. Like skin, the cornea is covered by a multi-layered epithelium forming a barrier to physical harm and invading microorganisms. But unlike the skin, when injury occurs the corneal epithelium is repaired by stem cells clustered in the tissue’s periphery, first by quickly dividing in great numbers and then by migrating towards the damaged site as matured epithelial cells in order to seal the wound.
However, this healing process can be compromised when injuries reach the stem cell niche. The research now published has important implications for developing new ways to heal this type of damage.
The director of this study and leader of the Tissue Engineering Lab at Newcastle University, Professor Che Connon, explained: “We can now prove that the cornea becomes stiffer when exposed to injuries such as those caused by what are commonly known as acid attacks, and demonstrate that wound healing is impaired due to stem cells differentiating in response to the stiffening of their otherwise soft niche, and not because they are killed during injury, as previously thought.”
“This is an exciting development in the field of corneal biology, and allows us to better understand how vision works. But even more important, it provides us with a new set of strategies to treat eye conditions which were until now inoperable. We call these less invasive strategies Biomechanical Modulation Therapies.”