Studies in Glaucomatous Optic Nerve Damage

青光眼是世界上导致失明的主要原因，目前影响着220万美国公民。 虽然降低眼压(IOP)的传统疗法可以稳定许多患者的视力， 其他人继续失去视力，尽管压力控制看起来很好。这表明独一无二的 青光眼可能会出现眼袋，这会使残留的视神经纤维越来越容易受到眼压的影响。 识别和了解这些变化将导致有效的新方法来预防视力丧失 青光眼，特别是在细胞死亡之前应用于视网膜细胞。 这一建议集中于这样一种假设，即高眼压和衰老都会损害视网膜的能力 神经节细胞(RGC)支持轴突细胞骨架的组织和轴突的运输、功能 对它们的生存至关重要。这将通过对大鼠视网膜内组织进行基因阵列分析来验证 高眼压模型(8个月大)，以确定这些生物的共同基因反应范围 回应。这些发现将通过定量逆转录聚合酶链式反应得到证实 (qrt-pcr)和免疫组织化学方法将蛋白产物定位于这一特定的细胞。 一层。将使用激光捕获显微切割技术识别RGC特异的基因变化 用荧光示踪剂和qRT-PCR标记RGC。这些基因变化的可逆性随后将在 眼压升高一段时间后通过睫状体脱离来降低眼压的眼睛。这些将是 通过基因芯片分析在视网膜内部进行评估，并通过qRT-PCR对RGC进行特异性评估。最后，qrt- 将在老年动物(28个月大)的组织中使用聚合酶链式反应来评估RGC基因对升高的反应 睫状体透析术使眼压正常化后眼压恢复情况。 与公众健康相关：这些实验将提供有关视网膜细胞机制的信息 青光眼的损害和视力丧失，一种疾病预计在下一年在美国增加50% 15年来，由于我们的人口迅速老龄化。这一知识将导致有效的新疗法，可以 在常规降压治疗的基础上，保护最有可能发生高血压的患者的视力 进展，如老年人和患有晚期疾病的人。

Glaucoma is a major cause of blindness in the world, and currently affects 2.2 million United States citizens. While conventional treatments to lower intraocular pressure (IOP) can stabilize vision in many patients, others continue to lose vision in spite of apparently good pressure control. This suggests that unique hanges may occur in glaucoma that leave remaining optic nerve fibers increasingly susceptible to IOP. Identifying and understanding such changes will lead to potent new methods of preventing vision loss in glaucoma, particularly if applied to retinal cells before they are committed to cell death. This proposal concentrates on the hypothesis that both elevated IOP and aging impair the ability of retinal ganglion cells (RGC) to support the organization of the axonal cytoskeleton and axonal transport, functions critical to their survival. This will be tested by performing gene array analysis on inner retinal tissue from a rat model (8 months old) of elevated IOP to determine the range of gene responses common to these biological responses. These findings will be confirmed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and immunohistochemistry will be used to localize protein products to the specific cells of this layer. Identification of gene changes specifically to RGC will be done using laser capture microdissection of RGC labeled by fluorescent tracers and qRT-PCR. Reversibility of these gene changes will then be tested in eyes in which pressure is lowered by cyclodialysis following an initial period of IOP elevation. These will be evaluated in the inner retina by gene array analysis and in RGC specifically with qRT-PCR. Finally, qRT- PCR will be used in tissue from aged animals (28 months old) to evaluate RGC gene responses to elevated IOP and their ability to recover following pressure normalization by cyclodialysis. Relevance to public health: These experiments will provide information on cellular mechanisms of retinal damage and visual loss in glaucoma, a disease expected to increase in the United States by 50% in the next 15 years due to rapid aging of our population. This knowledge will lead to effective new therapies that can be added to conventional pressure-lowering treatment to protect vision in patients at greatest risk of progression, such as the elderly and those with advanced disease.