Expression and Function of Members of the GDNF Family in the Human Cornea with Respect to Neublastin

Abstract

Abstract: : 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.

Keywords: cornea: basic science • wound healing • growth factors/growth factor receptors