New research suggests a new approach to understanding wound healing in the treatment of corneal and skin diabetic ulcers by closely examining the cellular and molecular mechanisms underlying diabetic peripheral neuropathy (DPN).
Occurring in more than 75% of diabetic patients, DPN is one of the earliest and most common pathological manifestations of diabetes. This condition can cause ulcerations in the cornea and skin.
“Using Streptozotocin-induced type I diabetes and cornea epithelial wounding experimental models, we made novel observations that may soon lead to innovative therapies to treat DPN and ulcerations of the cornea and skin in diabetic patients,” Fu-shin Yu, PhD, professor of ophthalmology and director of research at the Kresge Eye Institute of Wayne State University, said in a statement.
Researchers from the Wayne State University used post-wound corneal sensory degeneration and regeneration as a model for their report. During their investigation, they uncovered a similarity between diabetic mouse cornea and patients with DPN: the density of sensory nerve fibers and their endings are drastically reduced. Following wounding, the regenerative capacity of corneal nerves is impaired in the corneas of diabetic patients compared to normal B6 mouse corneas. This coincides with a reduction in the number of infiltrating dendritic cells in the wounded corneas of diabetic mice. The investigators also found that after wounding dendrictic cells guide the regenerating corneal sensory nerve fibers.
The study’s findings also showed that the application of ciliary neurotrophic factor (CNTF) can partially adverse effects of diabetes on sensory nerve and nerve regeneration. CNTFR-alpha (CNTFRα) may also be a valuable alternative to CNTF in treating neuron degenerative diseases such as DPN.
The report was funded by the National Eye Institute of the National Institutes of Health.
“In summary, our data show that diabetes disrupts DC-nerve communication in unwounded corneas and during wound healing, resulting in DPN or DNK,” the authors wrote. “These results suggest the potential of DC-based cell therapy, as autologous DCs can be readily prepared and manipulated to produce CNTF, and provide evidence for CNTF or its specific receptor CNTFRα as a therapeutic reagent for the treatment of DPN.”
Gao N, Yan C, Lee P, Sun H, Yu F. Dendritic cell dysfunction and diabetic sensory neuropathy in the cornea. J. Clin. Invest. 2016. doi:10.1172/jci85097.