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F.E. Kruse, S. Ebner, B. Erber, J. Pohl, P. Hanke, L. You; Expression and Function of Members of the GDNF Family in the Human Cornea with Respect to Neublastin . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3807.
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Purpose: Neurotrophins like NGF stimulate corneal wound healing and have been used for human treatment. In this study we determined presence and func-tion of various members of the (glia cell derived neurotrophic factor) GDNF-family and their receptors in the human cornea and evaluated functional significance. Methods: RT PCR was performed in ex vivo and cultured corneal epithelium and stroma. Expression of GDNF, neublastin, and their receptors GFRalpha-1, GFRalpha-2, as well as ret were investigated. Functional significance regarding neublastin was determined concerning proliferation and migration in serum-free clonal culture. Western blots were performed for MAP-kinase phosphorylation. Results: The corneal epithelium transcribes neublastin while GDNF was not present in the epithelium but in the stroma. Both epithelium and stroma also transcribes the ret receptor. Furthermore transcription of GFRalpha-1, was found in the epithelium. Both recombinant GDNF and neublastin enhanced corneal epithelial migration while the effect on clonal proliferation was less pronounced. GDNF and neublastin induced MAP-kinase phosphorylation. Conclusions: Our results indicate that members of the GDNF family belong to the normal inventory of cytokines that are used in the cross-talk between groups of epithelial cells and between epithelium and stroma. Together with the effect on migration GDNF and neublastin might be used for treatment of corneal wound healing disorders.
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