Lorber Barbara, Berry Martin, Logan Ann
Molecular Neuroscience Group, Division of Medical Sciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom.
J Neurosci Res. 2008 Mar;86(4):894-903. doi: 10.1002/jnr.21545.
We have investigated the differential mediators of the neurotrophic effects of intravitreal peripheral nerve grafting and lens injury on adult rat retinal ganglion cells (RGC). Lens injury and intravitreal peripheral nerve grafting both stimulated RGC neurite growth in vitro and axon regeneration past the optic nerve lesion site in vivo concomitant with activation of retinal glia and invasion of macrophages into the eye. These observations, together with the results of coculture studies using a macrophage-free intact peripheral nerve segment, a macrophage-free intact lens, a macrophage-rich peripheral nerve segment, or a macrophage-rich injured lens in retinal cultures suggest that the stimulation of RGC axon regeneration by lens injury and intravitreal peripheral nerve grafting share a common macrophage-derived component overlain by distinct lens-derived and peripheral nerve-derived neurotrophic factors, respectively. RGC axon regeneration following lens injury and intravitreal peripheral nerve grafting was similar in vivo, correlating with similar retinal glia activation whereas, in vitro, the level of RGC neurite outgrowth was significantly higher following intravitreal peripheral nerve grafting compared with lens injury, concomitant with the presence of increased numbers of activated retinal glia. This suggests that in vivo RGC axon regeneration induced by lens injury and peripheral nerve grafting may be limited, in part, by factors derived from activated retinal glia.
我们研究了玻璃体内植入外周神经和晶状体损伤对成年大鼠视网膜神经节细胞（RGC）神经营养作用的差异介导因子。晶状体损伤和玻璃体内植入外周神经均能在体外刺激RGC神经突生长，并在体内促进轴突再生越过视神经损伤部位，同时伴有视网膜神经胶质细胞的激活和巨噬细胞侵入眼内。这些观察结果，以及在视网膜培养中使用无巨噬细胞的完整外周神经段、无巨噬细胞的完整晶状体、富含巨噬细胞的外周神经段或富含巨噬细胞的损伤晶状体进行共培养研究的结果表明，晶状体损伤和玻璃体内植入外周神经对RGC轴突再生的刺激具有共同的巨噬细胞衍生成分，分别由不同的晶状体衍生和外周神经衍生的神经营养因子覆盖。晶状体损伤和玻璃体内植入外周神经后RGC轴突再生在体内相似，与相似的视网膜神经胶质细胞激活相关，而在体外，玻璃体内植入外周神经后RGC神经突生长水平明显高于晶状体损伤，同时伴有活化视网膜神经胶质细胞数量增加。这表明在体内，晶状体损伤和外周神经移植诱导的RGC轴突再生可能部分受到活化视网膜神经胶质细胞衍生因子的限制。
