University of Puerto Rico-Medical Sciences Campus, Anatomy and Neurobiology Department, Institute of Neurobiology, Puerto Rico.
J Chem Neuroanat. 2012 Dec;46(1-2):35-44. doi: 10.1016/j.jchemneu.2012.08.003. Epub 2012 Aug 25.
We have previously shown that application of fibroblast growth factor-2 (FGF-2) to cut optic nerve axons enhances retinal ganglion cell (RGC) survival in the adult frog visual system. These actions are mediated via activation of its high affinity receptor FGFR1, enhanced BDNF and TrkB expression, increased CREB phosphorylation, and by promoting MAPK and PKA signaling pathways. The role of endogenous FGF-2 in this system is less well understood. In this study, we determine the distribution of FGF-2 and its receptors in normal animals and in animals at different times after optic nerve cut. Immunohistochemistry and Western blot analysis were conducted using specific antibodies against FGF-2 and its receptors in control retinas and optic tecta, and after one, three, and six weeks post nerve injury. FGF-2 was transiently increased in the retina while it was reduced in the optic tectum just one week after optic nerve transection. Axotomy induced a prolonged upregulation of FGFR1 and FGFR3 in both retina and tectum. FGFR4 levels decreased in the retina shortly after axotomy, whereas a significant increase was detected in the optic tectum. FGFR2 distribution was not affected by the optic nerve lesion. Changes in the presence of these proteins after axotomy suggest a potential role during regeneration.
我们之前已经表明,应用成纤维细胞生长因子-2(FGF-2)于切断的视神经轴突可以增强成年青蛙视觉系统中的视网膜神经节细胞(RGC)存活。这些作用是通过激活其高亲和力受体 FGFR1、增强 BDNF 和 TrkB 表达、增加 CREB 磷酸化以及促进 MAPK 和 PKA 信号通路来介导的。内源性 FGF-2 在该系统中的作用了解较少。在这项研究中,我们确定了 FGF-2 及其受体在正常动物和视神经切断后不同时间点的动物中的分布。使用针对 FGF-2 及其受体的特异性抗体,通过免疫组织化学和 Western blot 分析,在对照视网膜和视顶盖中以及视神经损伤后 1、3 和 6 周进行了检测。FGF-2 在视网膜中短暂增加,而在视神经切断后仅 1 周时在视顶盖中减少。轴突切断诱导了 FGFR1 和 FGFR3 在视网膜和视顶盖中的长期上调。FGFR4 水平在轴突切断后不久在视网膜中下降,而在视顶盖中检测到显著增加。FGFR2 分布不受视神经损伤的影响。轴突切断后这些蛋白质的存在变化表明它们在再生过程中具有潜在的作用。