PDF(Pubmed)
Abstract：
Retinal ganglion cell (RGC) axons provide the only link between the light sensitive and photon transducing neural retina and visual centers of the brain. RGC axon degeneration occurs in a number of blinding diseases and the ability to stimulate axon regeneration from surviving ganglion cells could provide the anatomic substrate for restoration of vision. OTX2 is a homeoprotein transcription factor expressed in the retina and previous studies showed that, in response to stress, exogenous OTX2 increases the in vitro and in vivo survival of RGCs. Here we examined and quantified the effects of OTX2 on adult RGC axon regeneration in vitro and in vivo. The results show that exogenous OTX2 stimulates the regrowth of axons from RGCs in cultures of dissociated adult retinal cells and from explants of adult retinal tissue and that RGCs respond directly to OTX2 as regrowth is observed in cultures of purified adult rat RGCs. Importantly, after nerve crush in vivo, we observed a positive effect of OTX2 on the number of regenerating axons up to the optic chiasm within 14 days post crush and a very modest level of acuity absent in control mice. The effect of OTX2 on RGC survival and regeneration is of potential interest for degenerative diseases affecting this cell type. All animal procedures were approved by the local \"Comié d\'éιthique en expérimentation animale n°59\" and authorization n° 00702.01 delivered March 28, 2014 by the French \"Ministére de l\'enseignement supérieur et de la recherche\".
摘要：
视网膜神经节细胞（RGC）轴突提供了光敏和光子转导神经视网膜与大脑视觉中心之间的唯一联系。RGC轴突变性发生在许多致盲疾病中，从存活的神经节细胞刺激轴突再生的能力可以为恢复视力提供解剖基础。OTX2是一种在视网膜中表达的同源异型蛋白转录因子,为了应对压力，外源性OTX2增加RGC的体外和体内存活率。在这里，我们检查并量化了OTX2对体外和体内成年RGC轴突再生的影响。结果显示,外源OTX2刺激来自解离的成年视网膜细胞的培养物中的RGC和来自成年视网膜组织的外植体的轴突的再生长,并且RGC直接响应于OTX2,因为在纯化的成年大鼠RGC的培养物中观察到再生长。重要的是,在体内神经挤压后，我们观察到OTX2对挤压后14天内直至视神经交叉的再生轴突数量有积极影响,而对照小鼠的视神经交叉的视神经视神经视神经视神经视神经视神经视神经视神经视神经视神经视神经视神经视神经视神经视神经视神经视神经视神经视神经视神经视神经视神经视神经视神经视神经视神经视神经视神经视神经视神经视神经视神经视神经视神经OTX2对RGC存活和再生的影响对于影响这种细胞类型的退行性疾病具有潜在的意义。所有动物程序均由当地的“动物试验委员会n°59”批准，并由法国的“Ministeredel'enseignementsupérieuretdelarecherche”于2014年3月28日交付了第00702.01号授权。
