ADENOSINE AND RETINAL ISCHEMIA

腺苷和视网膜缺血

• 批准号: 6384388
• 负责人: STEVEN ROTH
• 金额: $ 20万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-01-01 至 2002-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6384388
• 关键词: adenosine; blood flow measurement; disease /disorder model; electroretinography; high performance liquid chromatography; histopathology; hypoxia; ischemia; laboratory rat; light microscopy; neurotransmitter metabolism; oxygen consumption; purinergic receptor; reperfusion; retina circulation; retina disorder

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.

描述（改编自申请人的摘要）：发生视网膜缺血 当视网膜的氧气和葡萄糖供应中断时。 这 病理生理学涉及细胞生物化学或能量水平的变化， 血流量和基因表达。 之前与该项目相关的工作有 除其他事项外，显示腺苷在 视网膜缺血再灌注损伤的病理生理学。 此外 证明了视网膜预处理现象，其中短暂的 长时间缺血前 24 或 72 小时的非损伤性缺血期 完全保留视网膜功能和形态。 出现这个过程 需要蛋白质合成，初步数据表明腺苷可能 是启动预处理的关键因素。 提议的实验 将使用生化、形态和功能测量来检查 腺苷对视网膜缺血的机制和作用。 长期目标 旨在表征针对缺血性损伤的内源性保护机制 并利用这些信息来开发临床相关的 视网膜缺血性疾病的治疗策略。 三个具体目标是 建议：（1）描述基本机制和局限性 预处理和腺苷作为引发剂的作用 预处理； (2) 检查腺苷代谢改变的影响 严重缺血时视网膜功能和结构的变化； (3) 测试 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相关，例如 视网膜动脉闭塞，或也导致的慢性疾病 缺血，例如糖尿病性视网膜病变。