Dendritic cell-based therapy shows promise treating diabetic peripheral neuropathy and ulcerations in the cornea and skin.
Recent research revealed a new understanding of the mechanisms in diabetic peripheral neuropathy (DPN), a condition that affects more than 75% of diabetic patients.
DPN can cause ulcerations in both the cornea and skin, leading to neuropathic pain and foot ulcerations that often require amputation. The development of DPN is unclear, mostly due to the lack of good available animal models.
The study, published in the Journal of Clinical Investigation, used the cornea — the most densely innervated mammalian tissue – as a model to study the underlying mechanisms of DPN.
“Using Streptozotocin-induced type 1 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,” said researcher Fu-Shin Yu, PhD.
The results of the study found that the density of sensory nerve fibers and their endings reduced significantly in the diabetic mouse cornea.
Additionally, the regenerative capacity of corneal nerves after wounding was impaired in the corneas of diabetic patients compared with normal B6 mouse corneas. This coincided with a reduction of infiltrating dendritic cells within the wounded corneas of diabetic mice, suggesting that sensory neuropathy is associated with a decrease in the dendritic cell population inside the diabetic cornea.
Dendritic cells were also found to act as guide for regenerating corneal sensory nerve fibers post-wounding, and is associated with the disruption in diabetic corneas.
In diabetic corneas, the impairment of sensory nerve regeneration is because of the decrease in ciliary neurotropic factor (CNTF). Also within a diabetic cornea, hyperglycemia disrupts DC-sensory nerve interactions, causing sensory nerve regeneration impairment after the wounding and diabetic peripheral neuropathy in the cornea.
The process is reversible, however, because the application of CNTF and CNTFR-alpha were able to partially reverse the adverse effects of diabetes on the sensory nerve and nerve regeneration.
Researchers believe that CNTFRa could be a valuable alternative to CNTF for treating patients with DPN and could increase the utilization of naturally produced CNTF without adverse events.
“These novel findings have potential to develop new dendritic cell-based cell therapy to treat diabetic peripheral neuropathy and ulcerations in the cornea and skin,” Yu said.