Bach Helene, Feldheim David A, Flanagan John G, Scalia Frank
Program in Anatomy and Cell Biology, State University of New York Health Science Center at Brooklyn, Brooklyn, New York 11203, USA.
J Comp Neurol. 2003 Dec 22;467(4):549-65. doi: 10.1002/cne.10941.
Many studies have demonstrated the involvement of the EphA family of receptor tyrosine kinases and their ligands, ephrin-A2 and -A5, in the development of the temporonasal axis of the retinotectal/collicular map, but the role of these molecules in optic nerve regeneration has not been well studied. Noting that the characteristic gradients of the EphA/ephrin-A family that are expressed topographically in the retina and tectum of embryonic chicks and mice tend to disappear after birth, we took as our starting point an analysis of EphA and ephrin-A expression in leopard frogs (Rana pipiens and utricularia), species capable of regenerating the retinotectal map as adults. For the EphA family to be involved in the regeneration, one would expect these topographic gradients to persist in the adult or, if downregulated after metamorphosis, to be reexpressed after optic nerve injury. Using EphA3 receptor and ephrin-A5 ligand alkaline phosphatase in situ affinity probes (RAP and LAP, respectively) in whole-mount applications, we report that reciprocally complementary gradients of RAP and LAP binding persist in the optic tract and optic tectum of postmetamorphic frogs, including mature adults. EphA expression in temporal retinal axons in the optic tract was significantly reduced after nerve section but returned during regeneration. However, ephrin-A expression in the tectal parenchyma was not significantly elevated by either eye removal, with degeneration of optic axons, or during regeneration of the retinotectal projection. Thus, the present study has demonstrated a persisting expression of EphA/ephrin-A family members in the retinal axons and tectal parenchyma that may help guide regenerating fibers, but we can offer no evidence for an upregulation of ephrin-A expression in conjunction with optic nerve injury.
许多研究已证明受体酪氨酸激酶EphA家族及其配体ephrin - A2和 - A5参与视网膜 - 顶盖/丘脑映射颞鼻轴的发育，但这些分子在视神经再生中的作用尚未得到充分研究。注意到在胚胎小鸡和小鼠的视网膜和顶盖中按拓扑结构表达的EphA/ephrin - A家族的特征梯度在出生后往往会消失，我们以分析豹蛙（豹纹蛙和囊蛙）中EphA和ephrin - A的表达为出发点，豹蛙是成年后能够再生视网膜 - 顶盖映射的物种。如果EphA家族参与再生，那么人们会预期这些拓扑梯度在成体中持续存在，或者如果在变态后下调，在视神经损伤后会重新表达。我们在整装标本中分别使用EphA3受体和ephrin - A5配体碱性磷酸酶原位亲和探针（分别为RAP和LAP），报告了RAP和LAP结合的相互补充梯度在变态后的青蛙，包括成熟成体的视束和视顶盖中持续存在。视束中颞侧视网膜轴突的EphA表达在神经切断后显著降低，但在再生过程中恢复。然而，无论是眼球摘除伴视神经轴突退变，还是在视网膜 - 顶盖投射再生过程中，顶盖实质中的ephrin - A表达均未显著升高。因此，本研究证明了EphA/ephrin - A家族成员在视网膜轴突和顶盖实质中持续表达，这可能有助于引导再生纤维，但我们没有证据表明ephrin - A表达会随着视神经损伤而上调。
