Diabetic cornea wounds produce significantly weaker electric signals that may contribute to impaired healing.
Wounds naturally produce electric signals which serve as powerful cues that stimulate and guide cell migration during wound healing. In diabetic patients, impaired wound healing is one of the most challenging complications in diabetes management. A fundamental gap in knowledge is whether diabetic wounds have abnormal electric signaling. Here we used a vibrating probe to demonstrate that diabetic corneas produced significantly weaker wound electric signals than the normal cornea. This was confirmed in three independent animal models of diabetes: db/db, streptozotocin-induced and mice fed a high-fat diet. Spatial measurements illustrated that diabetic cornea wound currents at the wound edge but not wound center were significantly weaker than normal. Time lapse measurements revealed that the electric currents at diabetic corneas lost the normal rising and plateau phases. The abnormal electric signals correlated significantly with impaired wound healing. Immunostaining suggested lower expression of chloride channel 2 and cystic fibrosis transmembrane regulator in diabetic corneal epithelium. Acute high glucose exposure significantly (albeit moderately) 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.
Department of Dermatology, University of California, Davis, CA, USA.|Bioelectromagnetics Laboratory, Department of Occupational and Environmental Health, School of Public Health, School of Medicine, Zhejiang University, Hangzhou, China.
Yunyun
Y
Shen
Department of Dermatology, University of California, Davis, CA, USA.
Trisha
T
Pfluger
Department of Dermatology, University of California, Davis, CA, USA.|Department of Biology, Centre of Molecular and Environmental Biology (CBMA), University of Minho, Braga, Portugal.
Fernando
F
Ferreira
Department of Biology, California State University, Northridge, CA, USA.
Jiebing
J
Liang
Department of Pharmacology, University of California, Davis, CA, USA.
Manuel F
MF
Navedo
Bioelectromagnetics Laboratory, Department of Occupational and Environmental Health, School of Public Health, School of Medicine, Zhejiang University, Hangzhou, China.
Qunli
Q
Zeng
Department of Dermatology, University of California, Davis, CA, USA.
Brian
B
Reid
Department of Dermatology, University of California, Davis, CA, USA.|Department of Ophthalmology and Vision Science, University of California, Davis, CA, USA.
Min
M
Zhao
D000818:Animals; D000090007:CLC-2 Chloride Channels; D018118:Chloride Channels / Q000378:metabolism*; D003316:Corneal Diseases / Q000378:metabolism / Q000503:physiopathology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D015536:Down-Regulation; D055724:Electrophysiological Phenomena; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D013311:Streptozocin; D014945:Wound Healing
D000090007:CLC-2 Chloride Channels; D018118:Chloride Channels; C000715428:Clcn2 protein, mouse; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D013311:Streptozocin