Project: Research project

Project Details


Following injury, whether it be the result of trauma, surgery, or
infection, the cornea utilizes a variety of cellular mechanisms to repair
itself. These events include reepithelialization, collagen repair via
keratocytes and endothelium, and repopulation of the endothelium in areas
in which it has been denuded. This process can be quite effective and
often leads to complete healing of the cornea with no associated visual
impairment. Unfortunately, the wound repair process can also result in
stromal edema, scarring, ulceration, or in the case of refractive
surgical procedures and penetrating keratoplasty, unpredictable and
possibly fluctuating refractive errors. To better understand and
possibly to better control the wound healing process, an understanding of
the basic cellular mechanisms of corneal wound healing is essential.

Ion channels in cellular membranes have been shown to be important
mediators in events such as cell activation, mitogenesis and cell
proliferation, migration, volume regulation, secretion, and responses to
growth factors. Because all of these events are involved in the response
of keratocytes and endothelial cells during the corneal wound healing
process, the understanding of the interaction between ion channels and
these events is crucial. Preliminary data shows that surgically wounded
rabbit corneal endothelial cells have different ionic currents than those
in the non-wounded control eye. Interestingly, these currents are
similar to those seen in cultured endothelial cells. In keratocytes,
preliminary data shows that fetal bovine serum stimulation, a known
"activator" of this cell type, causes a rapid increase in the amplitude
of the membrane currents. This effect appears to be associated with both
activation of a new channel type as well as the voltage sensitive Na+
channel. A similar current activation is observed when 8-bromo-cAMP is
added to the bath. The specific aims of this grant are designed to
specifically address the biophysical nature and physiological relevance
of many of these preliminary findings.

Initial studies will utilize whole cell and single channel patch clamp
techniques to characterize and determine the mechanisms of injury induced
changes in endothelium and keratocyte ion channel activity. In addition,
the physiological and pharmacological significance of these changes will
be examined using in-vivo wound healing studies as well as in-vitro
perfusion studies.
Effective start/end date9/30/925/31/99


  • Medicine(all)