Involvement of transcription factors in apoptosis of the Retinal Ganglion Cells by Optic Nerve Transection.

为了研究c-Jun和c-Jun n端磷酸化（JNP）在视神经（ON）横断后视网膜神经节细胞（RGCs）凋亡中的作用，我们在野生型小鼠和Jun的两个磷酸化受体丝氨酸突变为丙氨酸的小鼠（c-Jun[AA]小鼠）横断视神经后检测了c-Jun蛋白的表达、磷酸化和RGCs的凋亡。荧光示踪剂1,1'-二十八烷基-3,3,3',3'-四甲基吲哚高氯酸碳菁（DiI）涂于上丘（SC）， 7天后切断右侧ON。再过两周，计算每个区域的平均rgc数。在野生型小鼠视网膜神经节细胞层（GCL）检测到JNP和tunel标记的凋亡核，以响应ON横断。与野生型小鼠相比，c-Jun（AA）小鼠的tunel阳性细胞核数量减少。逆行标记显示，损伤后14天c-Jun（AA）小鼠损伤侧视网膜RGCs数量明显高于野生型小鼠。这些结果表明，JNP通过ON交易诱导RGCs凋亡有部分但显著的贡献。

To examine the involvement of c-Jun and c-Jun N-terminal phosphorylation (JNP) in apoptosis of retinal ganglion cells (RGCs) after the optic nerve (ON) transection, the expression and phosphorylation of c-Jun protein and apoptosis in RGCs were examined after ON transection in wild-type mice and mice in which both phosphoacceptor serines of Jun have mutated to alanines (c-Jun[AA] mice). The fluorescent tracer 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) was applied to the superior colliculi (SC), and the right ON was severed after 7 days. After two more weeks, the average number of RGCs per field was calculated. JNP and TUNEL-labeled apoptotic nuclei were detected in the ganglion cell layer (GCL) of the retina of the wild-type mice in response to ON transection. The numbers of TUNEL-positive nuclei in the c-Jun(AA) mice was reduced in comparison to those in wild-type mice. Retrograde labeling showed that the number of the RGCs in the retinas on the injured side of the c-Jun(AA) mice was significantly higher than in wild-type mice 14 days after the lesion. These results suggest that there is a partial but significant contribution of JNP to the induction of apoptosis m RGCs by ON transaction.