Neurotrophic factors (NTF) secreted by Schwann cells in a sciatic nerve (SN) graft promote retinal ganglion cell (RGC) axon regeneration after either transplantation into the vitreous body of the eye or anastomosis to the distal stump of a transected optic nerve. In this study, we investigated the neuroprotective and growth stimulatory properties of SN grafts in which Schwann cells had been killed (acellular SN grafts, ASN) or remained intact (cellular SN grafts, CSN). We report that both intravitreal (ivit) implanted and optic nerve anastomosed CSN promote RGC survival and when simultaneously placed in both sites, they exert additive RGC neuroprotection. CSN and ASN were rich in myelin-associated glycoprotein (MAG) and axon growth-inhibitory ligand common to both the central nervous system (CNS) and peripheral nervous system (PNS) myelin. The penetration of the few RGC axons regenerating into an ASN at an optic nerve transection (ONT) site is limited into the proximal perilesion area, but is increased >2-fold after ivit CSN implantation and increased 5-fold into a CSN optic nerve graft after ivit CSN implantation, potentiated by growth disinhibition through the regulated intramembranous proteolysis (RIP) of p75^NTR (the signalling trans-membrane moiety of the nogo-66 trimeric receptor that binds MAG and associated suppression of RhoGTP). Mϋller cells/astrocytes become reactive after all treatments and maximally after simultaneous ivit and optic nerve CSN/ASN grafting. We conclude that simultaneous ivit CSN plus optic nerve CSN support promotes significant RGC survival and axon regeneration into CSN optic nerve grafts, despite being rich in axon growth inhibitory molecules. RGC axon regeneration is probably facilitated through RIP of p75^NTR, which blinds axons to myelin-derived axon growth-inhibitory ligands present in optic nerve grafts.

中文翻译：

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玻璃体坐骨神经坐骨神经移植驱动视神经横断后视网膜神经节细胞的存活和轴突再生。

坐骨神经（SN）移植物中Schwann细胞分泌的神经营养因子（NTF）可以促进视网膜神经节细胞（RGC）轴突再生，既可以移植到眼玻璃体中，也可以吻合到横断视神经的远端残端。在这项研究中，我们研究了其中雪旺细胞已被杀死（无细胞SN移植物，ASN）或保持完整（细胞SN移植物，CSN）的SN移植物的神经保护和生长刺激特性。我们报告说两种玻璃体内（ivit）植入且视神经吻合的CSN促进了RGC的存活，当同时放置在两个部位时，它们可发挥加性RGC神经保护作用。CSN和ASN富含髓鞘相关糖蛋白（MAG）和中枢神经系统（CNS）和周围神经系统（PNS）髓鞘常见的轴突生长抑制配体。少数在视神经横断（ONT）处再生为ASN的RGC轴突的渗透仅限于近端灌注区域，但在ivit CSN植入后增加> 2倍，并在CSN视神经移植物中增加5倍后ivit CSN注入，由生长抑制解除通过P75的调节膜内蛋白水解（RIP）强化^NTR（nogo-66三聚体受体的信号跨膜部分，与MAG结合并抑制RhoGTP）。在所有处理后，Müller细胞/星形细胞都具有反应性，并且在同时进行ivit和视神经CSN / ASN移植后最大程度地变得活跃。我们得出的结论是，尽管ivit CSN加视神经CSN的支持可促进显着的RGC存活和轴突再生为CSN视神经移植物，尽管它富含轴突生长抑制分子。p75 ^NTR的RIP可能促进了RGC轴突的再生，这使轴突对视神经移植物中存在的髓磷脂衍生的轴突生长抑制配体不了解。