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

视网膜神经节细胞（Retinalganglioncells，RGC）是唯一能传递视觉信息的神经元 从视网膜到大脑与其他中枢神经系统（CNS）轴突一样，RGC轴突通常 损伤后不能再生，这是治疗视神经损伤患者的主要障碍。 神经损伤或青光眼以前，使用视神经挤压模型，我们和其他人已经表明， 不同的遗传干预诱导成年小鼠RGC轴突再生。但尽管 再生轴突的数量可观，视觉功能的恢复受到限制， 根本不存在一般认为，轴突再生本身不足以恢复 轴索损伤后视觉功能有意义的恢复。有证据表明髓鞘再生 促进跳跃传导是实现功能恢复的另一个关键步骤。 以前，不同的研究小组已经报道了再生的RGC轴突在多大程度上被破坏。 在成年小鼠中有髓鞘。然而，结果是可变的，提出了一种可能性， RGC轴突的髓鞘再生仅在某些条件下发生。总体而言，尚不清楚是否 存在诱导轴突再生和髓鞘再生的最佳干预。在这 我们将测试一个假设，即操纵某些基因和治疗方法将允许这两种情况发生。 轴突再生和髓鞘再生。在第一个目标，我们将确定是否再生研资局 在接受不同再生治疗的小鼠中轴突有髓鞘。第二个目标，我们 将决定髓鞘形成的程度是通过髓鞘形成促进治疗实现的。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有价值的信息， 在创伤或疾病后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.