Molecular Neuroscience Group, Neuropharmacology and Neurobiology Section, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
Neurobiol Dis. 2010 Feb;37(2):441-54. doi: 10.1016/j.nbd.2009.10.024. Epub 2009 Nov 10.
Intravitreal inflammation, induced by either lens injury, or intravitreal injection of zymosan (IVZ), protects RGC from apoptosis and stimulates axon regeneration after optic nerve transection. Here, we investigate the differential effects of intra-optic nerve zymosan (ONZ) and IVZ injections on RGC neuroprotection and axogenesis. After both IVZ and ONZ injection, zymosan-induced inflammation promoted a similar 4-/5-fold enhancement in RGC survival, compared to optic nerve transected controls, but only IVZ promoted RGC axon regeneration. IVZ was the most effective in activating retinal astrocyte/Müller cells while regulated intramembraneous proteolysis (RIP) of p75(NTR) and inactivation of Rho (key components of the axon growth inhibitory signalling cascade) occurred in both ONZ and IVZ, but only in the latter did RGC axons regenerate. We suggest that neuroprotective factors may be transported to RGC somata by retrograde transport after ONZ and diffuse into the retina after IVZ injection, but an axogenic agent is required to initiate and maintain disinhibited RGC axon regeneration that may be an exclusive property of a Müller cell-derived factor released after IVZ.
眼内炎症，无论是由晶状体损伤还是玻璃体内注射酵母聚糖（IVZ）引起的，都能保护 RGC 免于凋亡，并在视神经切断后刺激轴突再生。在这里，我们研究了视神经内注射酵母聚糖（ONZ）和 IVZ 注射对 RGC 神经保护和轴突发生的差异影响。与视神经切断对照相比，IVZ 和 ONZ 注射后，酵母聚糖诱导的炎症均促进了 RGC 存活的相似的 4-5 倍增强，但只有 IVZ 促进了 RGC 轴突再生。IVZ 最有效地激活视网膜星形胶质细胞/ Müller 细胞，而 p75（NTR）的调节跨膜蛋白水解（RIP）和 Rho 的失活（轴突生长抑制信号级联的关键组成部分）发生在 ONZ 和 IVZ 中，但只有后者 RGC 轴突再生。我们认为，神经保护因子可能在 ONZ 后通过逆行运输运输到 RGC 体，然后在 IVZ 注射后扩散到视网膜中，但需要轴发生因子来启动和维持去抑制的 RGC 轴突再生，这可能是 IVZ 释放的 Müller 细胞衍生因子的特有属性。
