Corneal Epithelial Wound Healing

Abstract

One of the Important functions of the cornea Is to maintain normal vision by refracting light onto the lens and retina. This property is dependent In part on the ability of the corneal epithelium to undergo continuous renewal. Epithelial renewal is essential because It enables this tissue to act as a barrier that protects the corneal Interior from becoming infected by noxious environmental agents. Furthermore, the smooth optical properties of the corneal epithelial surface are sustained through this renewal process. The rate of renewal Is dependent on a highly Integrated balance between the processes of corneal epithelial proliferation, differentiation, and cell death. One experimental approach to characterize these three aspects of the renewal process has been to study the kinetics and dynamlcs of corneal re-epithelializatlon In a wound-healing model. This effort has employed In vivo and In vitro studies. From such studies It Is evident that the appropriate Integration and coordination of corneal epithelial proliferation, adhesion, migration, and cell demise is dependent on the actions of a myriad of cytoklnes. Our goal here is to provide an overview into how these mediators and environmental tactors elicit control of eel-lUlar proliferation, adhesion, migration, and apoptosls. To this end we review the pertinent literature dealing with the receptor and the cell signaling events that are responsible for medi• atlng cytoklne control of corneal epithelial renewal. It Is our hope that a better appreciation can be obtained about the complexity of the control processes that are responsible for assuring continuous corneal epithelial renewal in health and disease.

Stress-induced corneal epithelial apoptosis mediated by K+ channel activation

“…However, there is currently very little information regarding how UV irradiation induces corneal epithelial cell apoptosis (Lu et al, 2001b). Recent studies provide cellular and molecular mechanisms involving hyperactivation of a K + channel in corneal epithelial cells Wang et al, 2003).…”

“…For example, we, as well as other researchers, have shown that stimulation of K + channel activity and dramatic loss of intracellular K + can result in apoptosis in the corneal epithelium, neurons, myeloblastic ML-1 cells, and other cell types (Schulz et al, 1996;Eldadah et al, 1997;Yu et al, 1997;Wang et al, 1999aWang et al, ,2003Lu et al, 2003;Trimarchi et al, 2002;Remillard and Yuan, 2004). It seems that there are dual functions of K + channels involving cell proliferation regulated by epidermal growth factor (EGF) (Lu et al, 2001a) and playing a role in mediating cell death induced by UV irradiation (Wang et al, 1999aLu et al, 2003). We found in corneal epithelial cells that K + channel activity is required for growth factor-stimulated activation of extracellularregulated kinase (ERK) (a MAP kinase) limb and proliferation.…”

“…The corneal epithelium on the surface of the cornea plays both important and functional roles in the vision system (Lu et al, 2001b). For example, it forms a physical barrier with multiple layers of cells to prevent noxious agents from infecting and damaging the eye.…”

Epigenetic silencing of maspin expression occurs early in the conversion of keratocytes to fibroblasts

“…When wounding occurs, the cornea sets into action various mechanisms to repair the injured area with the aim to maintain and/or restore optimum optical properties (Jester et al, 1999a). After wounding, epithelial cells migrate and proliferate to replace damaged cells (Lu et al, 2001). As a consequence of wounding of the epithelium and/or the stroma, the underlying anterior stromal cells undergo apoptosis, while corneal stromal cells distal from the wound undergo phenotypic changes to fibroblasts and myofibroblasts (Jester et al, 1987;Jester et al, 1996;Jester et al, 1999b;Maltseva et al, 2001).…”

Epidermal Growth Factor (EGF)-induced Corneal Epithelial Wound Healing through Nuclear Factor κB Subtype-regulated CCCTC Binding Factor (CTCF) Activation

“…The corneal epithelial layer protects the eye structures behind it from environmental insults and infections to maintain the intact function of the vision system (1). Corneal epithelial cells undergo a self-renewal process to replace the surface layer cells and repair corneal surface wounds dependent on the stimulation of growth factors.…”