Marín-Teva J L, Cuadros M A, Calvente R, Almendros A, Navascués J
Departamento de Biología Celular, Facultad de Ciencias, Universidad de Granada, E-18071 Granada, Spain.
J Comp Neurol. 1999 Sep 20;412(2):255-75.
We compared chronotopographical patterns of distribution of naturally occurring neuronal death in the ganglion cell layer (GCL) and the inner nuclear layer (INL) with patterns of tangential and radial migration of microglial precursors during quail retinal development. Apoptotic cells were identified by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling technique, and microglial precursors were identified by immunocytochemistry with an antibody recognizing quail microglial cells (QH1 antibody). Apoptotic cells were first detectable in the GCL at the seventh day of incubation (E7), were most abundant at E10, and were absent after E13. In the INL, apoptotic cells first appeared at E7, were most abundant at E12, and disappeared entirely after the third posthatching day (P3). In both retinal layers, cell death first appeared in a small central area of the retina and subsequently spread along three gradients: central-to-peripheral, temporal-to-nasal, and dorsal-to-ventral. The chronology of tangential (between E7 and E16) and radial migration (between E8 and P3) of microglial precursors was highly coincident with that of cell death in the GCL and INL. Comparison of the chronotopographical pattern of distribution of apoptotic nuclei in the GCL with the patterns of tangential and radial migration of microglial precursors neither supported nor refuted the hypothesis that ganglion cell death is the stimulus that triggers the entry and migration of microglial precursors in the developing retina. However, microglial cells in most of the retina traversed the INL only after cell death had ceased in this layer, suggesting that cell death in the INL does not attract microglial precursors migrating radially. Dead cell debris in this layer was phagocytosed by Müller cells, whereas migrating microglial cells were seen phagocytosing apoptotic bodies in the nerve fiber layer and GCL but not in the INL.
我们将鹌鹑视网膜发育过程中神经节细胞层(GCL)和内核层(INL)中自然发生的神经元死亡的时空分布模式,与小胶质细胞前体的切向和径向迁移模式进行了比较。通过末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸缺口末端标记技术鉴定凋亡细胞,并用识别鹌鹑小胶质细胞的抗体(QH1抗体)通过免疫细胞化学鉴定小胶质细胞前体。凋亡细胞在孵化第7天(E7)首次在GCL中被检测到,在E10时最为丰富,在E13后消失。在INL中,凋亡细胞在E7首次出现,在E12时最为丰富,并在孵化后第3天(P3)完全消失。在两个视网膜层中,细胞死亡首先出现在视网膜的一个小中央区域,随后沿三个梯度扩散:中央到周边、颞侧到鼻侧和背侧到腹侧。小胶质细胞前体的切向迁移(E7至E16)和径向迁移(E8至P3)的时间顺序与GCL和INL中的细胞死亡时间高度一致。将GCL中凋亡细胞核的时空分布模式与小胶质细胞前体的切向和径向迁移模式进行比较,既不支持也不反驳神经节细胞死亡是触发发育中视网膜中小胶质细胞前体进入和迁移的刺激因素这一假设。然而,大多数视网膜中的小胶质细胞仅在该层细胞死亡停止后才穿过INL,这表明INL中的细胞死亡不会吸引径向迁移的小胶质细胞前体。该层中的死亡细胞碎片被Müller细胞吞噬,而迁移的小胶质细胞则在神经纤维层和GCL中吞噬凋亡小体,但在INL中未观察到。