Fig. 1. The origin and effects of the wound-induced EF in rat cornea. (A) Simplified schematic representing the stratified rat corneal epithelium as a single layer of cells resting on a basement membrane and covered with a tear film. Cells are connected by tight junctions (brown squares), which form the major electrical resistive barrier of the epithelium. Intact mammalian corneal epithelium transports Na⁺ inwards (pink) and Cl^- outwards (blue) and this separation of charge establishes a transcorneal potential difference (TCPD) of around +40 mV (internally positive). At a wound (asterisk), ionic currents flow underneath the cell layers, pass through the lesion and have return paths in the tear fluid layer. This short-circuits the TCPD, which drops to 0 mV at the wound, but the TCPD remains at normal values 500 µm from the wound. This establishes a steady, laterally oriented EF (red arrows) directed towards the wound (Chiang et al., 1992). (B) The TCPD varies as a function of distance from the wound edge and we manipulated this pharmacologically. Control plot (red) represents directly measured data, with 100% of the normal TCPD present 500 µm from the wound edge (Chiang et al., 1992). The effects of various drugs are shown. For example, prostaglandin E2 (PGE2) increased the TCPD more than fourfold (425%). The drop off with distance to the wound is inferred by comparison to the no drug control graph. The x axis maps onto the diagrams in (A) and (C). PGE2 enhances chloride efflux, aminophylline and ascorbic acid inhibit phosphodiesterase breakdown of cAMP, which also enhances Cl^- efflux, AgNO₃ increases both early Na⁺ uptake and later Cl^- efflux. Ouabain inhibits the Na⁺/K⁺ ATPase and furosemide inhibits the active Cl^- efflux. (C) Detail of the wound in (A). The EF vector is defined as the flow of positive charge (red arrow). Current flows out the wound (asterisk), which acts as a cathode. Several cell behaviours close to the wound are directed by the wound-induced EF. Cell migration and nerve sprouting (green) are directed cathodally, towards the wound edge and mitotic spindles (green) align parallel to the EF. Cell division therefore also is oriented by the naturally occurring EF (Song et al., 2002).