Latest research identifies why people with diabetes take longer to recover from an eye wound compared to those without the condition.
Scientists from Cedars-Sinai Medical Center have discovered two related disease-associated changes to the cornea that they were previously unaware of.
In addition, they have also found some new therapeutic pathways that can reverse these changes and partially restore wound-healing function to the cornea.
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First author Dr Alexander Ljubimov said: “We have found that diabetes induces more cellular changes than we were aware of previously.
“The discovery does not affect gene sequence but entails specific DNA modifications altering gene expression – what are known as epigenetic alterations.”
According to the study, most diabetes drugs are not designed to treat molecular and cellular changes or their associated problems.
During the investigation, the researchers also detected the significance of Wnt-5a – a protein in charge of corneal wound healing and the function of stem cells.
Joint author Dr Ruchi Shah said: “Current treatments only address symptoms, so there is an urgent need to understand the molecular mechanisms of diabetes-related wound-healing problems.
“Understanding of this novel epigenetically regulated wound-healing mechanism could lead to therapeutic treatments that could help patients avoid further long-term ocular health issues.”
Approximately 70% of people with diabetes experience complications with the cornea – the transparent part of the eye that covers the iris and the pupil and allows light to enter the inside.
Advanced diabetes can impact the functioning of corneal stem cells. This means the cornea will take longer to recover after an eye injury or procedure, such as laser treatment for diabetic retinopathy or cataract surgery.
The research team examined the cornea cells from six people with diabetes and from five people with good eye health.
They found that the protein product of the WNT5A gene was repressed in the corneas of people with diabetes.
The cornea cells from people with diabetes also contained more microRNA molecules compared to those without the condition, the results have reported.
Throughout the investigation, the academics tested three interventions designed to normalise Wnt-5a protein expression.
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According to the study, they added the Wnt-5a protein directly, introduced a DNA methylation inhibitor and targeted microRNA levels with a novel gene therapy approach using a nanoscale compound.
Using synthetic molecules to block the microRNA, the scientists developed the compound as a substitute for a viral gene therapy they found to be toxic to stem cells.
The three therapeutic methods developed during the trial stimulated stem cell marker production and improved tissue regeneration, making wound healing faster.
Fellow researcher Dr Clive Svendsen said: “Novel therapies to reverse epigenetic effects could improve corneal function and may also prove significant in other diabetic complications. This work certainly helps move the field forward.”
To read the study, click here.
