Gene Therapy Shows Promise in Treating Diabetic Keratopathy

A new study has found that gene therapy of limbal cells can improve wound healing and restore stem cell marker patterns in human diabetic corneas. The research, conducted at the State University of New York, examined the effects of treating limbal cells with adenoviruses harboring full-length c-met mRNA or a mixture of adenoviruses with c-met and shRNA to MMP-10 and cathepsin F genes. The results showed that limbal c-met overexpression significantly accelerated healing of 8.5-mm epithelial wounds over EGFP controls.

Key Takeaways:

• The study used eight pairs of organ-cultured autopsy human diabetic corneas, with one cornea from each pair being treated with adenoviruses harboring full-length c-met mRNA or a mixture of adenoviruses with c-met and shRNA to MMP-10 and cathepsin F genes.
• The medium was kept at the limbal level to avoid transduction of central corneal epithelium, and fellow corneas received control adenoviruses with EGFP gene.
• After incubation for 5 or 10 days, central corneal epithelial debridement with n-heptanol was performed, and wound healing times were determined microscopically.
• Corneal cryostat sections were immunostained for diabetic and putative limbal stem cell markers, including alpha(3)beta(1) integrin, nidogen-1, fibronectin, laminin gamma 3 chain, Delta Np63 alpha, keratins 14, 15, and 17, as well as for activated signaling intermediates, phosphorylated EGFR, Akt, and p38.
• The results showed that limbal c-met overexpression significantly accelerated healing of 8.5-mm epithelial wounds over EGFP controls (6.3 days vs. 9.5 days, p < 0.05).
• Gene therapy of limbal epithelial stem cell compartment has a beneficial effect on the diabetic corneal wound healing and on diabetic and stem cell marker expression, and shows potential for alleviating symptoms of diabetic keratopathy.
• The study highlights the potential of gene therapy as a treatment for diabetic keratopathy, a condition that affects millions of people worldwide.

Statistics:

• 8.5-mm epithelial wounds healed in 6.3 days when treated with adenoviruses harboring full-length c-met mRNA, compared to 9.5 days for EGFP controls.
• P-value of <0.05 indicates statistical significance of the results.

Sources:

• Normalization of wound healing and stem cell marker patterns in organ-cultured human diabetic corneas by gene therapy of limbal cells. Experimental Eye Research, 2014;129():66-73.
• State University of New York, Dept. of Neurosci & Physiol, Syracuse, NY 13210, United States.