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New research led by scientists at Newcastle University, UK reveals a potential breakthrough for treating eye injuries and preventing blindness.

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 today 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.

Advanced microscopy unveils clues

This discovery was made possible by the development of a sophisticated microscopy technique that enables imaging of the physical properties of biological tissues at very high resolutions. Using this technology, 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.

“We also think our study is relevant to other scientific and medical fields beyond corneal research and can help the study, diagnostics, and treatment of diseases such as cancer, where tumor stiffening is a known marker of aggressive cancer cell behavior and of metastasis.”

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 behavior of the adult stem cells. Our imaging approach provides a valuable tool to analyze live cells within the cornea, as well as to further explore new therapies for restoring or even improving their function.”

The Cornea’s Repair Mechanisms

Many of the processes that keep the cornea 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 microorganisms. The corneal epithelium repairs injuries with 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 is 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.”

Developing a proof of concept

In the work, the researchers from Newcastle, collaborating with scientists at the University of Missouri, USA, also developed a proof-of-concept therapy to help restore corneal stem cell function and improve tissue regeneration following chemical eye burns.

Using live corneal tissues as a model system, the team recreated the effects of chemical burns. After treating the wounded, stiffened areas of the cornea using small and localized doses of collagenase, a tissue-softening enzyme to restore the stem cell niche, it once again became pliable and able to support stem cells and promote healing. This collagenase formulation has already been approved for related therapeutic applications by both the US Food and Drug Administration and the European Medicine Agency.

Dr. Gouveia added: “We show that the topical application of collagenase is safe and effective in restoring the normal stiffness of the cornea and helps tissue regeneration by preventing the differentiation and loss of adult stem cells after such injuries. We were further surprised to discover that the ability for a wound to heal was not directly caused by a lack of stem cells, but instead, due to the environment, these cells are exposed to. This really makes our therapy revolutionary.”

The scientists believe the same technique could be applied to help alleviate the lack of corneas available for transplantation by almost 5 million people suffering from total blindness due to corneal scarring caused by burns, lacerations, abrasion or disease.

In addition, ten million people worldwide are estimated to require surgery for preventing corneal blindness as a result of diseases such as trachoma, an infectious eye disorder affecting many people in developing countries. There is a real and pressing need for new therapies to treat these diseases which are both simple and cheap.

“We also think our study is relevant to other scientific and medical fields beyond corneal research and can help the study, diagnostics, and treatment of diseases such as cancer, where tumor stiffening is a known marker of aggressive cancer cell behavior and of metastasis.”

Sources: Newcastle University and Science Daily