Electric Currents are Weaker in Diabetic Wounds

A new study suggests that the slower healing associated with diabetic wounds could be the result of abnormal electric signaling.

Researchers at the University of California Davis (UCD; USA) used a highly sensitive probe to measure electrical fields in the corneas of eyes isolated from three mouse models with distinct types of diabetes: genetic (db/db), streptozotocin-induced, and mice fed a high-fat diet (HFD). The researchers used an eye model since the corneal epithelium actively maintains an electrical trans epithelial potential (TEP). Wounding collapses the local TEP, resulting in significant electric potentials, especially along the wound edges. Cells then migrate along the electric currents, closing the scratch wound in about 48 hours.

The researchers found that diabetic cornea wound currents at the wound edge (but not wound center) were significantly weaker than normal. Time-lapse measurements also revealed that electric currents in diabetic corneas lost normal rising and plateau phases, and that the abnormal electric signals correlated significantly with impaired wound healing. They also found by immunostaining a lower expression of chloride channel 2 and cystic fibrosis transmembrane regulator in the diabetic corneal epithelium. The study was published on June 10, 2016, in Nature Scientific Reports.

“This is the first demonstration, in diabetic wounds or any chronic wounds, that the naturally occurring electrical signal is impaired and correlated with delayed healing. Correcting this defect offers a totally new approach for chronic and non-healing wounds in diabetes,” said lead author professor of ophthalmology and dermatology Min Zhao, MD. “Acute high glucose exposure significantly reduced electrotaxis of human corneal epithelial cells in vitro, but did not affect the electric currents at cornea wounds. These data suggest that weaker wound electric signals and impaired electrotaxis may contribute to the impaired wound healing in diabetes.”

Wound repair is a precise and complex process necessary to recover tissue function after injury, which requires tightly controlled cell movement and tissue growth. Epithelial cells, including corneal epithelial cells (CECs) and skin keratinocytes, respond robustly by directional migration in electric fields, which override co-existing directional signals such as free edge and contact inhibition release. Electric fields applied as low as 12.5 mV/mm guide migration of CECs to the wound cathode, in the same direction as the wound electrical fields.

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