To examine the expression of P53-induced protein with a death domain (PIDD) at retina in animal model of optic nerve crush (ONC) and to investigate the role of PIDD in retinal glial activation and NF-κB activation induced by optic nerve damage, ONC animal model was established in Sprague–Dawley rats. PIDD has three isoforms (Isof); Western blot was performed to examine the expression of PIDD (Isof-1, Isof-2, and Isof-3, respectively) in retina at different time points after ONC. Retinal glial activation is closely associated with retinal neuronal death and is monitored by the expression of GFAP+ glial cells and IBA1+ microglia, then activated microglia leads to inflammatory cytokine production. NF-kB activation in glial cells also can promote neuronal death. In our study, the role of PIDD in retinal glial activation and NF-kB activation was investigated with PIDD inhibition selectively. PIDD expression (Isof-1 and Isof-3) was dramatically increased, and peaked at 3 days after ONC, while Isof-2 did not show any difference. In the ONC animal model, the number of GFAP+ glial cells and IBA1+ microglia in retinal layers was increased significantly, inflammatory cytokine production was upregulated, and NF-κB in glial cell was also activated. Moreover, those responses induced by optic nerve damage were attenuated with PIDD inhibition, which indicated that PIDD could regulate retinal glial activation, neuro-inflammation, and NF-κB activation. These results provided the direct demonstration that the PIDD (Isof-1and Isof-3) was overexpressed in retina after ONC, and PIDD may be involved in retinal neurodegenerative diseases by regulating retinal glial activation and NF-κB activation.

中文翻译：

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PIDD在视神经挤压后视网膜中的表达及其作用。

为了在视神经挤压伤（ONC）动物模型中检查视网膜上具有死亡域（PIDD）的P53诱导蛋白的表达，并研究PIDD在视神经损伤诱导的视网膜胶质细胞活化和NF-κB活化中的作用，在Sprague–Dawley大鼠中建立了ONC动物模型。PIDD具有三个同工型（Isof）；进行蛋白质印迹法以检查在ONC后不同时间点视网膜上PIDD的表达（分别为Isof-1，Isof-2和Isof-3）。视网膜胶质细胞活化与视网膜神经元死亡密切相关，并通过GFAP +胶质细胞和IBA1 +小胶质细胞的表达进行监测，然后活化的小胶质细胞导致炎症性细胞因子的产生。胶质细胞中的NF-kB激活也可以促进神经元死亡。在我们的研究中 通过选择性地抑制PIDD，研究了PIDD在视网膜胶质激活和NF-kB激活中的作用。PIDD表达（Isof-1和Isof-3）显着增加，并在ONC后3天达到峰值，而Isof-2没有任何差异。在ONC动物模型中，视网膜层中的GFAP +胶质细胞和IBA1 +小胶质细胞的数量显着增加，炎性细胞因子的产生上调，并且胶质细胞中的NF-κB也被激活。而且，由PIDD抑制减弱了由视神经损伤引起的反应，这表明PIDD可以调节视网膜神经胶质激活，神经炎症和NF-κB激活。这些结果直接证明了ONC后视网膜中的PIDD（Isof-1和Isof-3）过表达，