Optic nerve regeneration: translational studies

总结 视神经如果受伤就不能再生，留下创伤性或缺血性神经损伤或变性的受害者。 视网膜病变，如永久性视力丧失的青光眼。我们最近找到了一些方法， 通过激活视网膜神经节细胞（RGC）的内在生长状态来逆转这种情况， 眼睛的皱纹。当暴露于肿瘤调节蛋白（Ocm）时， 缺乏pten基因并具有升高水平的cAMP能够通过肠内途径再生受损的轴突， 疲劳的视神经，通过视交叉，并进入适当的目标领域，在那里他们形成突触和部分。 恢复视觉反应。我们现在建议开发将这些发现转化为 适合临床应用。我们将开发和测试腺相关病毒来表达OCM， 细胞内cAMP水平，并抵消轴突生长的细胞内和细胞外抑制剂。这些 研究将提高我们增强视神经再生的能力，可能帮助许多受害者。 创伤性或退行性视觉障碍。本文开发的方法和试剂也可用于 恢复中枢神经系统其他部分的神经回路。 !! ! !

Summary The optic nerve cannot regenerate if injured, leaving victims of traumatic or ischemic nerve damage or degen- erative diseases such as glaucoma with permanent visual losses. We have recently identified ways to partially reverse this situation by activating the intrinsic growth state of retinal ganglion cells (RGCs), the projection neu- rons of the eye. When exposed to oncomodulin (Ocm), a growth factors produced by inflammatory cells, RGCs lacking the pten gene and having elevated levels of cAMP are able to regenerate injured axons through the en- tire optic nerve, across the optic chiasm, and into appropriate target areas, where they form synapses and par- tially restore visual responses. We now propose to develop ways to translate these findings into methods that are suitable for clinical application. We will develop and test adeno-associated viruses to express Ocm, elevate intracellular levels of cAMP, and counteract cell-intrinsic and cell-extrinsic inhibitors of axon growth. These studies will increase our ability to augment regeneration in the optic nerve, potentially helping many victims of traumatic or degenerative visual disorders. The methods and reagents developed here may also be useful for restoring neural circuits in other parts of the CNS. !! ! !