GLAUCOMATOUS OPTIC NERVE DAMAGE

青光眼是视神经纤维死亡致盲的主要原因。 一种特有的模式。尽管许多因素可能会影响这一点 过程中，眼压升高是最好的记录和 所有的青光眼治疗都是针对控制眼压的。尽管 其中，对神经细胞和神经胶质细胞的了解相对较少。 对高眼压的反应，很大程度上是由于缺乏可靠的、 廉价的压力性视神经损伤动物模型。 最近已经在老鼠身上建立了这样的模型。选择性注射 硬化剂进入眼表血管使用特别设计的 微针会导致房水流出通道的疤痕， 产生可测量的眼压升高和可识别的视神经纤维 死亡。这项建议将改进技术，以生产温和和 严重的压力在不同的动物群体中上升。关联的 神经损伤将使用组织学、自动神经纤维 计数和免疫组织化学显示其与人类的关系 青光眼视神经病变。 努力分析哺乳动物对高眼压的细胞反应 视神经和视网膜将从研究蛋白质存在的变化开始 并用免疫组织化学方法对各种井进行了分布 具有神经元和神经胶质细胞成分的特征，其中大部分是 表现为对受伤的反应发生变化。初步研究将集中在 在眼压严重升高的眼睛上。检测到的蛋白质变化将是 用原位杂交确认和澄清 寡核苷酸探针，或核探针，以检测证据 信息产生过程中的细胞变化。Northern印迹分析也将 用于提供半定量的分析，尽管 它们的主要用途将是验证探针的特异性。 一旦特定蛋白质的可靠变化在眼睛中被定义 严重的眼压升高，这些标志物将被用来澄清确切的 眼压在引起神经损伤中的作用 严重眼压升高及早期与长期治疗效果的比较 眼压升高。这些研究有助于将这些变化确立为标记 未来对影响青光眼的其他因素的研究 过程，它们如何影响视神经对眼压的敏感性，以及它们如何 可能会被改变以保护青光眼患者的视神经。

Glaucoma is a major cause of blindness in which optic nerve fibers die in a characteristic pattern. Although many factors may influence this process, elevated intraocular pressure (IOP) is the best documented and all glaucoma therapy is directed at controlling eye pressure. In spite of this, relatively little is known about the neuronal and glial cell response to elevated IOP, due in large part to the lack of a reliable, inexpensive animal model of pressure-induced optic nerve damage. Such a model has recently been created in rats. Selective injection of sclerosing agents into ocular surface vessels using a specially designed microneedle causes scarring of the aqueous humor outflow pathways, producing measurably increased IOP and identifiable optic nerve fiber death. This proposal will refine the technique to produce mild and severe pressure rises in separate groups of animals. The associated nerve damage will be studied using histology, automated nerve fiber counts and immunohistochemistry to demonstrate its relationship to human glaucomatous optic neuropathy. Efforts to analyze the cellular response to elevated IOP in the mammalian optic nerve and retina will begin by studying changes in protein presence and distribution using immunohistochemistry for a variety of well characterized neuronal and glial cell components, most of which have been shown to change in response to injury. Initial studies will concentrate on eyes with severe IOP elevation. Protein changes detected will then be confirmed and clarified using in situ hybridization with either synthetic oligodeoxynucleotide probes, or riboprobes, to detect evidence for cellular changes in message production. Northern blot analysis will also be used to provide semiquantitative analyses, where indicated, although their primary use will be in verifying probe specificity. Once reliable changes in specific proteins are defined in eyes with severe IOP elevation, these markers will be used to clarify the exact role of IOP in causing nerve damage by comparing eyes with mild and severe IOP elevations and comparing the effects of early versus prolonged IOP rise. These studies win serve to establish these changes as markers for future studies of the other factors that influence the glaucomatous process, how they affect optic nerve susceptibility to IOP and how they might be altered to protect the optic nerve in glaucoma.