Neuroscience and Ophthalmology, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, B15 2TT, UK.
Cells. 2020 May 27;9(6):1335. doi: 10.3390/cells9061335.
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 () 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 CSN implantation and increased 5-fold into a CSN optic nerve graft after CSN implantation, potentiated by growth disinhibition through the regulated intramembranous proteolysis (RIP) of p75 (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 and optic nerve CSN/ASN grafting. We conclude that simultaneous 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, which blinds axons to myelin-derived axon growth-inhibitory ligands present in optic nerve grafts.
雪旺细胞分泌的神经营养因子（NTF）可促进视网膜神经节细胞（RGC）轴突再生，方法是将其移植到玻璃体或吻合到横断视神经的远端残端。在这项研究中，我们研究了雪旺细胞被杀死的（去细胞雪旺细胞，ASN）或保持完整的（细胞雪旺细胞，CSN）雪旺细胞移植的神经保护和生长刺激特性。我们报告说，眼内植入的和吻合的 CSN 均可促进 RGC 存活，当同时放置在两个部位时，它们会产生累加的 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）髓鞘共有的轴突生长抑制配体。在视神经横断（ONT）部位，只有少数 RGC 轴突再生进入 ASN，其穿透仅限于近病变区，但在植入 CSN 后增加了 >2 倍，在植入 CSN 后增加了 5 倍，这是通过调节跨膜蛋白水解（RIP）p75 来抑制生长（p75 是与 MAG 结合并抑制 RhoGTP 的神经生长抑制蛋白-66 三聚体受体的信号转导跨膜部分）。所有治疗后，Müller 细胞/星形胶质细胞都会发生反应，同时植入 CSN 和视神经 CSN/ASN 后反应最强烈。我们的结论是，尽管 CSN 富含轴突生长抑制分子，但同时植入 CSN 加视神经 CSN 支持可显著促进 RGC 存活和轴突再生到 CSN 视神经移植物中。RGC 轴突再生可能是通过 RIP p75 来促进的，该过程使轴突对存在于视神经移植物中的髓鞘衍生的轴突生长抑制配体失去敏感性。
