NMR STUDIES OF PRERETINAL NEOVASCULARIZATION

视网膜前新生血管化的核磁共振研究

• 批准号: 2163944
• 负责人: BRUCE A. BERKOWITZ
• 金额: $ 22.46万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-03-01 至 1998-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2163944
• 关键词: angiogenesis; blood vessel occlusion; eye fundus photography; fluorescein angiography; glucose metabolism; histology; hypoxia; immature animal; ischemia; laboratory rat; lactates; magnetic resonance imaging; nuclear magnetic resonance spectroscopy; oximetry; oxygen tension; retina circulation

The proliferation of new preretinal blood vessels into the vitreous is a major cause of visual loss in a number of common eye diseases. Although certain endogenous growth factors play a role in this neovascularization (NV), recent evidence indicates these growth factors are constantly available in the retina. In addition, NV is often associated with focal retinal areas of ischemia and it is presumed that a metabolic trigger (for example hypoxia, elevated glucose utilization and lactate concentration, or increased blood flow) activates the ambient growth factors and stimulates the initiation of NV. It has not been possible however, to establish the actual role of a specific metabolic factor in the trigger and regulation of NV since these factors are interdependent processes. We hypothesize that the stimulus of NV is an ischemia-related trigger, such as a significant perturbation (either singly or in combination) of retinal oxygen level, glucose utilization, lactate concentration, and retinal blood flow, which causes the ambient growth factors to become efficacious. To date, direct evaluation of the quantitative contributions of these interdependent factors has been lacking because it has not been possible to perform experiments in which various metabolic signals can be noninvasively assessed over long periods of time following controlled induction of NV. We have developed multinuclear nuclear magnetic resonance (NMR) techniques that circumvent these technical problems and can simultaneously record from intact tissue the quantitative contributions of oxygen level, glucose utilization, and lactate concentration prior to and during the development of NV in the same animal. We propose to employ these newly-developed NMR methods in a rat pup model of NV to answer the following question during the onset and progression of NV: What are the quantitative contributions of metabolic factors (preretinal oxygen level, lactate concentration, glucose utilization, and retinal blood flow) to the development and progression of NV? We will manipulate the occurrence of NV in our model and measure changes in the metabolic factors in relationship to: a) the spatial location of NV on retina; b) the occurrence and severity of the NV; c) changes in the occurrence of NV over time. These experiments will demonstrate the quantitative contributions of these metabolic factors and whether or not that are predictive of the occurrence of NV in this model.

新的前血管扩散到玻璃体中是 许多常见的眼科疾病中视觉丧失的主要原因。虽然 某些内源性生长因子在这种新血管中起作用 （NV），最近的证据表明这些增长因素一直是 可在视网膜上找到。此外，NV通常与焦点有关 缺血的视网膜区域，并假定是代谢触发的（对于 例如缺氧，葡萄糖利用率升高和乳酸浓度， 或增加血流）激活环境生长因子和 刺激NV的启动。但是，不可能 确定特定代谢因子在触发中的实际作用 和NV的调节，因为这些因素是相互依存的过程。 我们假设NV的刺激是与缺血相关的触发器， 例如重要的扰动（单一或组合） 视网膜氧气水平，葡萄糖利用率，乳酸浓度和 视网膜血流，这导致环境生长因子成为 有效。迄今为止，直接评估定量贡献 这些相互依存的因素缺乏，因为它不是 可以执行各种代谢信号的实验 在受控之后，长期评估了无创的 诱导NV。我们已经开发了多核核磁共振 （NMR）绕过这些技术问题的技术 同时记录完整组织的定量贡献 氧气水平，葡萄糖利用和乳酸浓度 在同一动物中NV的发展过程中。 我们建议在大鼠幼犬模型中采用这些新开发的NMR方法 NV在发作和进展过程中回答以下问题 NV：代谢因素的定量贡献是什么 （前氧气水平，乳酸浓度，葡萄糖利用和 视网膜血流）到NV的发展和发展？我们将 操纵NV在我们的模型中的发生，并衡量 与：a）NV的空间位置有关的代谢因素 视网膜b）NV的发生和严重性； c）变化 随着时间的流逝，NV发生。这些实验将证明 这些代谢因素的定量贡献以及是否 可以预测该模型中NV的发生。