Cohen-Cory S, Escandón E, Fraser S E
Division of Biology, Beckman Institute, California Institute of Technology, Pasadena 91125, USA.
Dev Biol. 1996 Oct 10;179(1):102-15. doi: 10.1006/dbio.1996.0244.
The temporal patterns of BDNF and trkB expression in the developing Xenopus laevis tadpole, and the responsiveness of retinal ganglion cells to BDNF, both in culture and in vivo, suggest significant roles for this neurotrophin during visual system development (Cohen-Cory and Fraser, Neuron 12, 747-761, 1994; Nature 378, 192-196, 1995). To examine the potential roles of this neurotrophin within the developing retina and in its target tissue, the optic tectum, we studied the cellular sites of BDNF expression by in situ hybridization. In the developing optic tectum, discrete groups of cells juxtaposed to the tectal neuropil where retinal axons arborize expressed BDNF, supporting the target-derived role commonly proposed for this neurotrophin. In the retina, retinal ganglion cells, ciliary margin cells, and a subset of cells in the inner nuclear layer expressed the BDNF gene. The expression of BDNF coincided with specific trkB expression by both retinal ganglion cells and amacrine cells, as well as with the localization of functional BDNF binding sites within the developing retina, as shown by in situ hybridization and BDNF cross-linking studies. To test for a possible role of endogenous retinal BDNF during development, we studied the effects of neutralizing antibodies to BDNF on the survival of retinal ganglion cells in culture. Exogenously administered BDNF increased survival, whereas neutralizing antibodies to BDNF significantly reduced baseline retinal ganglion cell survival and differentiation. This suggests the presence of an endogenous retinal source of neurotrophic support and that this is most likely BDNF itself. The retinal cellular patterns of BDNF and trkB expression as well as the effects of neutralizing antibodies to this neurotrophin suggest that, in addition to a target-derived role, BDNF plays both autocrine and/or paracrine roles during visual system development.
在非洲爪蟾蝌蚪发育过程中脑源性神经营养因子（BDNF）和酪氨酸激酶受体B（trkB）的表达时间模式，以及视网膜神经节细胞在体外培养和体内对BDNF的反应性，表明这种神经营养因子在视觉系统发育过程中发挥着重要作用（Cohen-Cory和Fraser，《神经元》12卷，747 - 761页，1994年；《自然》378卷，192 - 196页，1995年）。为了研究这种神经营养因子在发育中的视网膜及其靶组织视顶盖中的潜在作用，我们通过原位杂交研究了BDNF表达的细胞位点。在发育中的视顶盖中，与视网膜轴突分支的顶盖神经毡相邻的离散细胞群表达BDNF，支持了通常认为这种神经营养因子具有靶源性作用的观点。在视网膜中，视网膜神经节细胞、睫状缘细胞和内核层的一部分细胞表达BDNF基因。BDNF的表达与视网膜神经节细胞和无长突细胞中trkB的特异性表达以及发育中视网膜内功能性BDNF结合位点的定位相一致，原位杂交和BDNF交联研究表明了这一点。为了测试内源性视网膜BDNF在发育过程中可能发挥的作用，我们研究了BDNF中和抗体对体外培养的视网膜神经节细胞存活的影响。外源性给予BDNF可提高存活率，而BDNF中和抗体则显著降低视网膜神经节细胞的基线存活率和分化率。这表明存在内源性视网膜神经营养支持源，并且最有可能就是BDNF本身。BDNF和trkB在视网膜中的细胞表达模式以及这种神经营养因子中和抗体的作用表明，除了靶源性作用外，BDNF在视觉系统发育过程中还发挥自分泌和/或旁分泌作用。
