Modulating endogenous electric currents in human corneal wounds--a novel approach of bioelectric stimulation without electrodes

Abstract

Purpose: To measure electric current in human corneal wounds and test the feasibility of pharmacologically enhancing the current to promote corneal wound healing.

Methods: Using a noninvasive vibrating probe, corneal electric current was measured before and after wounding of the epithelium of donated postmortem human corneas. The effects of drug aminophylline and chloride-free solution on wound current were also tested.

Results: Unwounded cornea had small outward currents (0.07 μA/cm²). Wounding increased the current more than 5 fold (0.41 μA/cm²). Monitoring the wound current over time showed that it seemed to be actively regulated and maintained above normal unwounded levels for at least 6 hours. The time course was similar to that previously measured in rat cornea. Drug treatment or chloride-free solution more than doubled the size of wound currents.

Conclusions: Electric current at human corneal wounds can be significantly increased with aminophylline or chloride-free solution. Because corneal wound current directly correlates with wound healing rate, our results suggest a role for chloride-free and/or aminophylline eyedrops to enhance healing of damaged cornea in patients with reduced wound healing such as the elderly or diabetic patient. This novel approach offers bioelectric stimulation without electrodes and can be readily tested in patients.

FIGURE 1

Mounting and measuring from cornea. A, Cornea mounted in artificial anterior chamber for measurements with vibrating probe. B, Microscope view of wound on corneal surface. Dots show the different measuring positions which are plotted in Figure 2B. Scale bar, 1 mm.

FIGURE 2

Wound currents. A, Wounding cornea induces significantly increased outward currents (n = 14; *P < 0.002). B, Current is maximal at wound edge, dropping significantly outside wound (#P < 0.004).

FIGURE 3

Time-dependent changes in wound current. A, Wound edge currents are actively modulated. Open symbol at time zero shows current before wounding. After wounding current rises rapidly, levels off for a time, then declines slowly (n = 3). The pattern of change is very similar to that in rat cornea (inset; data from Reid et al, 2005). B, Overlaying human (open diamond symbols) and rat (closed circles) time course data shows the similar pattern of change over time. The rat data were scaled in the x axis to match the human data time points and scaled in the y axis so that the prewound (time zero) time points overlapped, and the maximum value from each trace (human: 0.41 mA at 45 minutes; rat: 11.19 mA at 40 minutes) were at the same level.

FIGURE 4

Enhancing wound currents. Wound edge current was significantly increased in chloride-free solution (n = 6) or aminophylline (10 mM; n = 4). * and # P < 0.004.