RETINAL GANGLION CELL AXON-TARGET INTERACTIONS

我的研究的长期目标是了解引导 视网膜神经节细胞轴突沿着视束并引导它们 适当的目标区域。 这笔赠款的具体目的是 理解（i）目标（即，上级丘）影响 神经节细胞和不断增长的视神经轴突和（ii）如何扩散的因素 来源于受神经支配的靶区域可能受到调控。 整体 这些实验要检验的假设是， 由视网膜轴突神经支配后由上级丘释放 影响视网膜神经节的存活和突起生长 细胞 这些问题将通过体外研究来解决， 使用神经移植的进一步研究以及检查 营养因子基因在上级丘的表达 发展 第一组研究将考察 移植靶区对视神经轴突的影响 生长：胶原凝胶培养物中或基质上的视网膜外植体 用细胞粘附分子L1包被，将与 上级丘，以测试是否以前神经支配的目标 影响视神经轴突生长。 一项平行的研究将审查是否 体内的视神经轴突被吸引到异位靶。 第二组 的研究将检查靶源性因素对视网膜病变的影响， 神经节细胞：第一个将使用视网膜神经节细胞生物测定， 体外测试无神经支配的上级条件培养基 丘（来源于神经支配前的正常小鼠或先天性的 盲小鼠）缺乏存在于 第二项研究将使用原位杂交技术 将上级丘中的BDNF mRNA水平与视神经轴突相关联 输入. 虽然这些研究的主要目标是解决一个基本的 发展问题（了解视网膜神经节细胞如何 轴突与其目标相互作用），这些研究也有直接的 对形成视神经连接的治疗努力研究的影响 受损或有缺陷的视觉系统

The long-term goal of my research is to understand the factors that guide retinal ganglion cell axons along the optic tract and which direct them to appropriate target regions. The specific aim of this grant is to understand (i) how the target (i.e., the superior colliculus) affects ganglion cells and growing optic axons and (ii) how diffusible factors derived from innervated target regions might be regulated. The overall hypothesis to be tested by these experiments is that diffusible factors released by the superior colliculus upon innervation by retinal axons influence the survival of and neurite outgrowth from retinal ganglion cells. These issues will be addressed with in vitro studies, with further studies using neural transplants and in studies which examine the expression of trophic factor genes in the superior colliculus during development. The first group of studies will examine the ability of explanted and transplanted target regions to influence optic axon outgrowth: retinal explants in collagen gel cultures, or on substrates coated with the cell-adhesion molecule L1, will be co-cultured with superior colliculus to test whether previously innervated targets influence optic axon outgrowth. A parallel study will examine whether optic axons in vivo are attracted to an ectopic target. A second group of studies will examine the effects target-derived factors on retinal ganglion cells: the first will use a retinal ganglion cell bioassay to test in vitro whether media conditioned by non-innervated superior colliculus (derived from pre-innervation normal mice or congenitally blind mice) lacks a protein that is present in the active fraction of innervated SC. The second study will use in situ hybridization techniques to correlate BDNF mRNA levels in the superior colliculus with optic axon input. Although the main goal of these studies is to address a basic developmental question (an understanding of how retinal ganglion cell axons interact with their target), these studies also have direct implications for studies on therapeutic efforts to form optic connections in damaged or deficient visual systems.