Soto Ileana, López-Roca Teresa, Blagburn Jonathan M, Blanco Rosa E
Institute of Neurobiology and Department of Anatomy, University of Puerto Rico Medical Sciences Campus, 201 Boulevard del Valle, San Juan, Puerto Rico.
Brain Res. 2006 Aug 4;1103(1):65-75. doi: 10.1016/j.brainres.2006.05.062. Epub 2006 Jun 30.
We have shown previously that application of fibroblast growth factor-2 (FGF-2) to the cut optic nerve of the frog, Rana pipiens, augments the survival of retinal ganglion cells (RGCs). In this study, we examine the effects of axotomy and FGF-2 treatment upon the distribution of nitric oxide synthase (NOS) and NADPH diaphorase (NADPH-d) activity in the frog retina and tectum. We find that NOS and NADPH-d are largely absent from RGCs but present in amacrine neurons and in retinorecipient tectal layers. Axotomy alone has little effect on NOS expression or diaphorase activity, apart from slightly increasing the levels of expression in a subpopulation of amacrine cells that arborize in the On sublamina of the inner plexiform layer. FGF-2 application to the optic nerve down-regulates NOS expression and activity in the retina and up-regulates it in the tectum, particularly in retinorecipient layers. Electron microscopy of the optic nerve and neurofilament immunostaining of the tectum suggests that FGF-2 treatment increases the number of regenerating retinal axons arriving at the tectum. The effects in the retina and tectum are probably indirect, that in the retina being due to retrograde signaling from RGCs to amacrine neurons, and that in the tectum being due to re-induction of NOS expression in tectal neurons by the arrival of regenerating axons. At this stage, it appears unlikely that these changes in NOS play a role in the FGF-2's survival effect on RGCs.
我们之前已经表明，将成纤维细胞生长因子2（FGF-2）应用于牛蛙（Rana pipiens）切断的视神经上，可提高视网膜神经节细胞（RGCs）的存活率。在本研究中，我们检测了轴突切断术和FGF-2处理对牛蛙视网膜和视顶盖中一氧化氮合酶（NOS）分布及NADPH黄递酶（NADPH-d）活性的影响。我们发现，RGCs中基本不存在NOS和NADPH-d，但无长突神经元以及视网膜接受层中存在这些物质。单独的轴突切断术对NOS表达或黄递酶活性影响很小，只是略微增加了在内网状层On亚层中分支的一类无长突细胞亚群的表达水平。将FGF-2应用于视神经会下调视网膜中NOS的表达和活性，并上调视顶盖中的表达和活性，尤其是在视网膜接受层。对视神经的电子显微镜检查以及对视顶盖的神经丝免疫染色表明，FGF-2处理增加了到达视顶盖的再生视网膜轴突的数量。视网膜和视顶盖中的这些影响可能是间接的，视网膜中的影响是由于RGCs向无长突神经元的逆行信号传导，而视顶盖中的影响是由于再生轴突的到达对视顶盖神经元中NOS表达的重新诱导。在这个阶段，这些NOS的变化似乎不太可能在FGF-2对RGCs的存活作用中发挥作用。
