Investigators from Cedars-Sinai have provided new understanding of how diabetes delays wound healing in the eye, identifying for the first time two related disease-associated changes to the cornea.
The findings, published in the peer-reviewed journal Diabetologia, also identified three therapeutic pathways that reversed these changes and partially restored wound-healing function to the cornea—a discovery that could ultimately inform new treatments for diabetes.
The new research also identifies for the first time an important role of Wnt-5a, a secreted signaling protein investigators found responsible for corneal wound healing and the function of stem cells—cells capable of differentiating into many cell types.
To identify the epigenetic changes discovered in this study—changes not hard-wired into the genome from birth, but introduced later—the researchers compared cells from the corneas from six diabetic patients with those of five healthy donors. They found that in diabetic corneas, the protein product of the WNT5A gene was repressed. Additionally, in diabetic samples, they found an increase in the microRNA that inhibits WNT5A.
Investigators will continue to analyze their data to better understand the mechanisms of WNT5A and other genes related to wound healing. They are also studying a combination therapy to target both microRNA and DNA methylation in hopes that it will more thoroughly normalize wound healing by increasing Wnt-5a protein.