Assessing Axonal Fate, Myelination and Visual Function Recovery after New Gene Treatment

视网膜神经节细胞(RGC)是唯一传递视觉信息的神经元类型 从视网膜到大脑。与其他中枢神经系统(CNS)轴突一样，RGC轴突一般 损伤后不能再生，这是治疗视神经患者的主要障碍 神经损伤或青光眼。此前，使用视神经挤压模型，我们和其他人已经展示了 不同的基因干预诱导成年小鼠RGC轴突再生。然而，尽管 相当数量的再生轴突，视功能的恢复受到限制或 根本不存在。一般认为，仅靠轴突再生是不足以恢复的 轴突损伤后视功能有意义的恢复。有证据表明，再髓鞘形成 促进跳跃传导是实现功能恢复的另一个关键步骤。 此前，不同的研究小组报告了再生的RGC轴突的程度 成年小鼠有髓鞘。然而，结果是多变的，这增加了一种可能性，即 RGC轴突的再髓鞘形成只有在特定条件下才会发生。总体而言，尚不清楚 有一种诱导轴突再生和重新髓鞘形成的最佳干预措施。在这 提案中，我们将检验一个假设，即操纵某些基因和治疗方法将允许 轴突再生和再髓鞘形成。在第一个目标中，我们会决定再生的研资局 在接受不同再生治疗的小鼠中，轴突是有髓的。在第二个目标中，我们 将决定促进髓鞘形成治疗达到的髓鞘形成程度。结果 从这些研究中获得的信息将为开发未来的治疗方法提供宝贵的信息 在创伤后或在疾病中再生受损的视网膜轴突。

Retinal ganglion cells (RGCs) are the only neuronal type that relays visual information from the retina to the brain. Like other central nervous system (CNS) axons, RGC axons generally do not regenerate following damage, presenting a major obstacle for treating patients with optic nerve trauma or glaucoma. Previously, using optic nerve crush model, we and others have shown that different genetic interventions induce RGC axon regeneration in adult mice. However, despite the considerable numbers of regenerated axons, recovery of visual function has been limited or non-existent. It is generally viewed that axon regeneration alone is not enough to restore meaningful recovery of visual functions after axonal injury. Evidence indicates that remyelination facilitating saltatory conduction is another key step toward attaining functional restoration. Previously, different groups have reported the extent to which regenerated RGC axons are myelinated in adult mice. However, the results have been variable, raising a possibility that remyelination of RGC axons occurs only under certain conditions. Overall, it is unclear whether there is an optimal intervention for inducing both axon regeneration and remyelination. In this proposal, we will test a hypothesis that manipulating certain genes and treatments will permit both axon regeneration and remyelination. In the first aim, we will determine whether regenerated RGC axons are myelinated in the mice receiving different regenerative treatments. In the second aim, we will determine the degree to myelination is attained with myelinating-promoting treatment. Results obtained from these studies will provide valuable information on developing future therapies to regenerate injured retinal axons after trauma or in diseases.