Study identifies how diabetes slows eye healing

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 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.

To identify the epigenetic changes discovered in this study—changes not hard-wired into the genome from birth, but introduced later the team 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.

The team of scientists then induced wounds to corneal cells in culture and corneal organ cultures, and tested three interventions designed to normalize Wnt-5a protein expression. They added the Wnt-5a protein directly; they introduced a DNA methylation inhibitor, originally approved to treat cancer; and they targeted microRNA levels with a novel gene therapy approach using a nanoscale compound. The team developed the compound, which uses synthetic molecules to block the microRNA, as a substitute for a viral gene therapy they found to be toxic to stem cells.

All three therapeutic methods, in the diabetic samples, stimulated stem cell marker production and improved tissue regeneration, accelerating wound healing.

Reference: Reversal of dual epigenetic repression of non‑canonical Wnt‑5a normalises diabetic corneal epithelial wound healing and stem cells, Diabetologia, DOI 10.1007/s00125-023-05960-1