Department of Physiology, Genetics, Microbiology, University of Alicante, Spain.
Exp Eye Res. 2011 Mar;92(3):227-37. doi: 10.1016/j.exer.2010.12.001. Epub 2010 Dec 11.
Aim of this study was to examine synaptic connectivity changes in the retina and the location and rate of apoptosis in transgenic S334ter line-3 and line-5 rats with photoreceptor degeneration. Heterozygous S334ter-line-3 and line-5 at P11-13, P30, P60, P90 and several control non-dystrophic rats (Long Evans and Sprague-Dawley) at P60, were studied anatomically by immunohistochemistry for various cell and synaptic markers, and by PNA and TUNEL label.- S334ter line-3 exhibited the fastest rate of degeneration with an early loss of photoreceptors, with 1-2 layers remaining at P30, and only cones left at P60. Line-5 had 4-5 layers left at P30, and very few rods left at P60-90. In both lines, horizontal cell processes (including dendrites and axon) were diminished at P11-13, showing gaps in the outer plexiform layer (OPL) at P60, and at P90, almost no terminal tips could be seen. Bipolar cells showed a retraction of their dendrites forming clusters along the OPL. Synaptic terminals of A-II amacrine cells in the IPL lost most of their parvalbumin-immunoreactivity. The apoptosis rate was different in both lines. Line-3 rats showed many photoreceptors affected at P11, occupying the innermost part of the outer nuclear layer. Line-5 showed a lower number of apoptotic cells within the same location at P13. In summary, the S334ter line-3 rat has a faster progression of degeneration than line-5. The horizontal and bipolar terminals are already affected at P11-P13 in both models. Apoptosis is related to the mutated rhodopsin transgene; the first photoreceptor cells affected are those close to the OPL.
本研究旨在研究转 S334ter 线-3 和线-5 型大鼠视网膜中突触连接变化以及感光细胞变性中的凋亡位置和速度。在 P11-13、P30、P60、P90 时，对杂合 S334ter-line-3 和 line-5 大鼠以及几个非进行性变性的对照大鼠（Long Evans 和 Sprague-Dawley）进行解剖学研究，用各种细胞和突触标志物的免疫组织化学方法，以及用 PNA 和 TUNEL 标记进行研究。- S334ter line-3 显示出最快的变性速度，感光细胞早期丢失，P30 时仅剩 1-2 层，P60 时仅剩视锥细胞。Line-5 在 P30 时仍有 4-5 层，P60-90 时仅剩极少数视杆细胞。在这两种系中，P11-13 时水平细胞过程（包括树突和轴突）减少，P60 时外丛状层（OPL）出现间隙，P90 时几乎看不到终末尖端。双极细胞的树突回缩，沿着 OPL 形成簇。内节层（IPL）中的 A-II 无长突细胞的突触末端失去了大部分副甲状腺球蛋白免疫反应性。两种系的凋亡率不同。Line-3 大鼠在 P11 时已有许多感光细胞受到影响，占据外核层的最内层。Line-5 在同一位置 P13 时显示出较少的凋亡细胞。总之，S334ter line-3 大鼠的变性进展比 line-5 大鼠更快。两种模型中的水平和双极末端在 P11-P13 时已经受到影响。凋亡与突变视紫红质转基因有关；受影响的第一批感光细胞是靠近 OPL 的细胞。
