ADENOSINE AND RETINAL ISCHEMIA

描述(摘自申请者的摘要)：发生视网膜缺血 当视网膜的氧气和葡萄糖供应中断时。这个 病理生理学涉及细胞生化或能量水平的变化， 血流和基因表达。之前与该项目相关的工作有 在其他方面显示，腺苷复杂地参与了 视网膜缺血再灌注损伤的病理生理学研究。此外， 视网膜预适应的现象被展示出来，由此短暂的 长时间缺血前24或72小时的非损伤性缺血期 保存完好的视网膜功能和形态。此时将显示此过程 需要蛋白质的合成和初步数据显示，腺苷可能 是启动预适应的关键因素。建议的实验 将使用生化、形态和功能测量来检查 腺苷抗视网膜缺血的机制和作用。长期目标 是表征针对缺血损伤的内源性保护机制 并利用这些信息发展出临床上相关的 视网膜缺血性疾病的治疗策略。三个具体目标是 建议：(1)描述基本机制和限制 预适应与腺苷作为血管紧张素转换酶启动剂的作用 预适应；(2)检测腺苷代谢改变的影响 严重缺血时视网膜功能和结构的改变；(3)检测 腺苷受体介导的视网膜保护机制 缺血性损伤。这些研究与急性疾病状态有关，例如 视网膜动脉阻塞，或慢性疾病，也会导致 缺血，如糖尿病视网膜病变。

DESCRIPTION (Adapted from applicant's abstract): Retinal ischemia occurs when the oxygen and glucose supply to the retina is interrupted. The pathophysiology involves changes in cellular biochemistry or energy level, blood flow and gene expression. Previous work related to this project has shown, among other things, a complex involvement of adenosine in the pathophysiology of retinal ischemia-reperfusion injury. In addition the phenomenon of retinal pre-conditioning was demonstrated, whereby a brief period of non-damaging ischemia 24 or 72 hours before prolonged ischemia completely preserved retinal function and morphology. This process appears to require protein synthesis and preliminary data shows that adenosine may be a key factor in the initiation of preconditioning. Proposed experiments will use biochemical, morphological and functional measurements to examine mechanisms and effects of adenosine on retinal ischemia. The long-term goal is to characterize endogenous protective mechanisms against ischemic injury in the retina and to use this information to develop clinically relevant treatment strategies of retinal ischemic diseases. Three specific aims are proposed: (1) to characterize basic mechanisms and limitations of preconditioning and the role of adenosine as an initiator of preconditioning; (2) to examine the effect of altered adenosine metabolism in retinal function and structure during severe ischemia; and (3) to test mechanisms of adenosine receptor-mediated protection against retinal ischemic injury. These studies are relevant to acute disease states such as retinal arterial occlusion, or to chronic diseases that also result in ischemia, such as diabetic retinopathy.