Lindqvist Niclas, Peinado-Ramónn Paloma, Vidal-Sanz Manuel, Hallböök Finn
Department of Neuroscience, Unit for Developmental Neuroscience, Uppsala University, Uppsala, Sweden.
Exp Neurol. 2004 Jun;187(2):487-99. doi: 10.1016/j.expneurol.2004.02.002.
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.
在本研究中，我们研究了视神经横断前后视网膜 - 顶盖系统中胶质细胞源性神经营养因子（GDNF）及其受体Ret、GFRalpha1和GFRalpha2的表达情况。通过逆行神经元示踪与原位杂交相结合的方法，我们发现Ret和GFRalpha1在13 - 14%的视网膜神经节细胞（RGCs）中表达。这些表达Ret的RGCs无法被确定属于RG(A)、RG(B)和RG(C)任何一种特定的亚型。在这些RGCs中，Ret与脑源性神经营养因子受体TrkB共表达。视神经横断导致视网膜中Ret mRNA水平降低，而GDNF、GFRalpha1和GFRalpha2 mRNA水平升高。给予GDNF蛋白可支持轴突切断的RGCs。对视神经正常的上丘（SC）分析未显示GDNF mRNA的任何表达，但损伤后SC中的GDNF mRNA水平升高。总之，这些发现确定了一部分RGCs可能是GDNF直接作用模式下药物治疗的靶点。正常SC中未检测到GDNF mRNA，这对GDNF作为成年RGCs在SC中产生的靶源性因子的作用提出了质疑。结果支持GDNF在视网膜局部发挥作用，并且作为损伤诱导系统的一部分，可能对内源性GDNF配体和外源性给予的配体都起到增强神经保护和神经再生反应的作用。
