Guidance Molecules in Retinal Axon Regeneration

描述(申请人提供)：视觉是我们重要的感官之一，在我们的许多行为中起着核心作用。成人视觉系统将光信息转换为意识感知的能力是由于视网膜和中枢神经系统(CNS)靶标之间高度组织的神经连接。这些特定的连接是在胚胎发育期间形成的，因为被称为轴突的神经细胞过程从视网膜出来，并在胚胎大脑中导航，找到合适的靶点。这种路径发现涉及轴突顶端的受体蛋白，这些受体蛋白可以感知周围环境中存在的引导分子。引导分子的感应导致视网膜轴突加速、减速或改变其生长方向。胚胎视觉系统自我组装的这种非凡能力在成年动物身上消失了，在成年动物中，由于创伤或疾病造成的视网膜轴突损伤通常会导致永久性视力残疾。在前期工作中，我们发现了一些轴突引导分子，通常存在于胚胎视神经中，在损伤后的成年神经中发现。在这项提议中，我们测试了最初参与视神经发育的轴突引导分子和受体在受损的成年神经中重新表达的假设。此外，这些引导分子通过影响成年视网膜轴突的生长能力，在视觉系统损伤后的再生失败中发挥作用。拟议的研究将更全面地识别在受损视神经中发现的视网膜轴突引导分子，并表征它们对成年轴突生长是抑制还是促进作用。此外，我们将研究改变这些反应的方法，并进行体内研究，以确定轴突引导分子在视神经损伤后的功能作用。总之，这些研究将有助于为制定促进视网膜轴突再生和损伤和疾病后功能恢复的策略奠定基础。

DESCRIPTION (provided by applicant): Vision is one of our important senses and plays a central role in much of our behavior. The ability of the adult visual system to convert light information into conscious perception is due to highly organized neural connections between the retina and central nervous system (CNS) targets. These specific connections are formed during embryonic development as nerve cell processes called axons emerge from the retina and navigate within the embryonic brain to find their way to appropriate targets. This path finding involves receptor proteins on axon tips that sense guidance molecules present in the surrounding environment. The sensing of guidance molecules causes retinal axons to speed up, slow down, or change their direction of growth. This remarkable ability of the embryonic visual system to assemble itself is lost in the adult animal where retinal axon injury from trauma or disease often leads to permanent visual disability. In preliminary work, we have discovered that a number of axon guidance molecules, normally present in the embryonic optic nerve, are found in the adult nerve after injury. In this proposal, we test the hypothesis that axon guidance molecules and receptors originally involved in optic nerve development are re-expressed in the injured adult nerve. Furthermore, these guidance molecules play a role in regenerative failure after injury to the visual system by influencing the ability of adult retinal axons to grow. The proposed studies will more fully identify the retinal axon guidance molecules found in the injured optic nerve and characterize whether they have inhibitory or stimulatory effects on adult axon growth. In addition, we will investigate methods to modify these responses and perform in vivo studies to define the functional role of axon guidance molecules after optic nerve injury. Together, these studies will help establish a foundation for developing strategies to promote retinal axon regeneration and functional recovery after injury and disease.