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(Investigative Ophthalmology and Visual Science. 2003;44:244-249.)
© 2003 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.02-0456
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Electric Fields and MAP Kinase Signaling Can Regulate Early Wound Healing in Lens Epithelium

Entong Wang,1 Min Zhao,1 John V. Forrester,2 and Colin D. McCaig1

1From the Department of Biomedical Sciences, Institute of Medical Sciences, and the 2Department of Ophthalmology, Medical School, University of Aberdeen, Aberdeen, Scotland, United Kingdom.

PURPOSE. To use lens epithelial cell monolayer wounds as a model system for the aberrant cell migration underlying posterior capsule opacification (PCO) and to investigate the effects of an applied physiological electric field (EF) on monolayer wound healing.

METHODS. Scratch wounds were made in cultured bovine lens epithelial monolayers, and the wounds were exposed to an EF, with or without U0126 treatment (an inhibitor of active extracellular signal-regulated kinase [ERK 1/2]). Serial wound images were taken and wound areas were measured. Western blot analysis and immunocytochemical staining for ERK 1/2 in the wounded monolayers were performed.

RESULTS. An applied EF of a given polarity influenced the healing of lens epithelial monolayer wounds. Wounds facing the anode healed at normal rates, those facing the cathode closed much more slowly. U0126, an inhibitor of mitogen-activated protein kinase (MAPK) signaling, inhibited wound healing, with or without exposure to an EF. Western blot analysis showed that both wounding and application of an EF enhanced the activation of ERK 1/2 independently and that U0126 completely inhibited these activations of ERK 1/2 in monolayers. Immunocytochemical staining showed an asymmetric activation of ERK 1/2 in EF-exposed wounds, with much weaker fluorescence in cathode-facing wounds, which could contribute to differentially directed wound-healing rates in an EF.

CONCLUSIONS. Exposure to an EF inhibited the healing of lens epithelial monolayer wounds facing the cathode. ERK signaling pathways were involved in healing of lens epithelial monolayer wounds and in the EF-directed migration of the wound edge. It may be possible to use an applied EF to regulate the aberrant migration of lens epithelial cells that results in PCO after cataract surgery.




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