GDNF, Ret, GFRalpha1 and 2 in the adult rat retino-tectal system after optic nerve transection

Abstract

In the present study, we have studied the expression of glial cell line-derived neurotrophic factor (GDNF) and its receptors Ret, GFRalpha1, and GFRalpha2 in the retino-tectal system before and after optic nerve transection. Using retrograde neuronal tracing in combination with in situ hybridization, we found that Ret and GFRalpha1 are expressed by 13-14% of the retinal ganglion cells (RGCs). These Ret-expressing RGCs could not be identified as belonging to any particular of the RG(A), RG(B), and RG(C) sub types. Ret is co-expressed with the brain-derived neurotrophic factor receptor TrkB in these RGCs. Optic nerve transection resulted in reduced Ret mRNA levels in retina, while the levels of GDNF, GFRalpha1, and 2 mRNA increased. Administration of GDNF protein supported the axotomized RGCs. Analysis of normal superior colliculus (SC) did not show any expression of GDNF mRNA, yet GDNF mRNA levels in SC increased after injury. Together, these findings identify a portion of RGCs as being possible targets for pharmacological treatment with GDNF in a direct mode of action. The absence of detectable GDNF mRNA in normal SC questions the role for GDNF as being a target-derived factor produced in the SC for adult RGCs. The results support a function for GDNF locally in the retina and as part of an injury-induced system that may act to enhance neuroprotective and neuroregenerative responses both to endogenous GDNF ligands and those administered exogenously.