In the central nervous system (CNS), three types of myelin-associated inhibitors (MAIs) exert major inhibitory effects on nerve regeneration: Nogo-A, myelin-associated glycoprotein (MAG), and oligodendrocyte-myelin glycoprotein (OMgp). MAIs have two co-receptors, Nogo receptor (NgR) and paired immunoglobulin-like receptor B (PirB). Existing studies confirm that inhibiting NgR only exerted a modest disinhibitory effect in CNS. However, the inhibitory effects of PirB on nerve regeneration after binding to MAIs are controversial too. We aimed to further investigate the effect of PirB knockdown on the neuroprotection and axonal regeneration of retinal ganglion cells (RGCs) after optic nerve injury in rats. The differential expression of PirB in the retina was observed via immunofluorescence and western blotting after 1, 3, and 7 days of optic nerve injury (ONI). The retina was locally transfected with adeno-associated virus (AAV) PirB shRNA, then, the distribution of virus in tissues and cells was observed 21 days after AAV transfection to confirm the efficiency of PirB knockdown. Level of P-Stat3 and expressions of ciliary neurotrophic factor (CNTF) were detected via western blotting. RGCs were directly labeled with cholera toxin subunit B (CTB). The new axons of the optic nerve were specifically labeled with growth associated protein-43 (GAP43) via immunofluorescence. Flash visual evoked potential (FVEP) was used to detect the P1 and N1 latency, as well as N1-P1, P1-N2 amplitude to confirm visual function. PirB expression in the retina was significantly increased after ONI. PirB knockdown was successful and significantly promoted P-Stat3 level and CNTF expression in the retina. PirB knockdown promoted the regeneration of optic nerve axons and improved the visual function indexes such as N1-P1 and P1-N2 amplitude. PirB is one of the key molecules that inhibit the regeneration of the optic nerve, and inhibition of PirB has an excellent effect on promoting nerve regeneration, which allows the use of PirB as a target molecule to promote functional recovery after ONI.

中文翻译：

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大鼠视神经损伤后的轴突再生可以通过视网膜中的 PirB 敲低来改善

在中枢神经系统 (CNS) 中，三种髓鞘相关抑制剂 (MAI) 对神经再生发挥主要抑制作用：Nogo-A、髓鞘相关糖蛋白 (MAG) 和少突胶质细胞髓鞘糖蛋白 (OMgp)。MAI 有两个共同受体，Nogo 受体 (NgR) 和配对免疫球蛋白样受体 B (PirB)。现有研究证实，抑制 NgR 仅对 CNS 产生适度的去抑制作用。然而，PirB 与 MAI 结合后对神经再生的抑制作用也存在争议。我们旨在进一步研究 PirB 敲低对大鼠视神经损伤后视网膜神经节细胞 (RGC) 的神经保护和轴突再生的影响。PirB 在视网膜中的差异表达在 1、3、3 天后通过免疫荧光和蛋白质印迹法观察到。和 7 天的视神经损伤 (ONI)。视网膜局部转染腺相关病毒（AAV）PirB shRNA，然后，在AAV转染后21天观察病毒在组织和细胞中的分布，以确认PirB敲低的效率。通过蛋白质印迹检测P-Stat3的水平和睫状神经营养因子（CNTF）的表达。RGC 直接用霍乱毒素亚基 B​​ (CTB) 标记。视神经的新轴突通过免疫荧光用生长相关蛋白 43 (GAP43) 特异性标记。闪光视觉诱发电位（FVEP）用于检测 P1 和 N1 潜伏期，以及 N1-P1、P1-N2 振幅以确认视觉功能。ONI后视网膜中的PirB表达显着增加。PirB 敲低是成功的，并显着促进了视网膜中 P-Stat3 的水平和 CNTF 的表达。PirB 敲低促进视神经轴突的再生，改善视功能指标如 N1-P1 和 P1-N2 振幅。PirB是抑制视神经再生的关键分子之一，抑制PirB对促进神经再生有极好的作用，这使得可以使用PirB作为靶分子来促进ONI后的功能恢复。