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F.E. Kruse, T. Dietrich, M. Zenkel, A. Ohlmann, J. Joergensen, U. Schloetzer–Schrehardt; Role of Glial Cell Derived Neurotrophic Factors in Corneal Epithelial Wound Healing . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2723.
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Existing data suggest that neurotrophic factors, such as nerve growth factor (NGF), modulate wound healing properties of the cornea. The glial cell–line–derived neurotrophic factor (GDNF) family includes four members, GDNF, neurturin, artemin, and persephin, which signal through specific GDNF family receptor subunits, termed GFRalpha1–4. This study investigates the hypothesis that GDNF plays an additional role in corneal (patho)physiology and is involved in corneal epithelial migration and wound healing.
Expression of the artemin receptor GFRalpha3 was investigated by immunohistochemistry using epitope–specific anti–mouse and anti–human GFRalpha3 antibodies and by quantitative Real–Time PCR in human and murine corneal and limbal specimens, in primary cultures of human corneal epithelial cells and keratocytes, and in a human corneal epithelial cell line. The effect of artemin (1 µg/ml) on corneal epithelial migration and re–epithelialization was assessed in epithelial debridement wound healing experiments using an in vitro organ culture system. The extent of corneal wound closure was examined at different intervals after debridement by fluorescein staining.
In addition to a prominent staining of corneal nerves, GFRalpha3 could be immunolocalized to corneal and limbal epithelial cells, to corneal keratocytes, and to single cells in the limbal stroma in both human and murine corneas with the various antibodies used. GFRalpha3 mRNA was weakly expressed in human corneal and limbal epithelium and stroma as well as in cultured keratocytes, and moderately expressed in cultured corneal epithelial cells. Corneal epithelial wound healing experiments demonstrated a significantly accelerated wound closure in corneas exposed to artemin as compared to control corneas. Whereas the epithelium of the corneas treated with artemin was completely closed 24 hr post–debridement, 30 to 50% of the wound area still remained defective at 48h post–debridement in the controls.
These results indicate that, in addition to NGF, members of the GDNF family of neurotrophins may play a role in corneal physiology/pathophysiology and may be involved in modulation of corneal epithelial migration and wound healing.
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