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.

视网膜前新生血管进入玻璃体是一种 在一些常见的眼病中，视力丧失的主要原因。虽然 某些内源性生长因子在这种新生血管中发挥作用。 (NV)，最近的证据表明，这些增长因素不断 在视网膜中可用。此外，NV经常与焦点联系在一起 视网膜缺血区，据推测，代谢触发(对于 例如低氧，葡萄糖利用率和乳酸浓度升高， 或血流增加)激活周围的生长因子并 刺激NV的启动。然而，它不可能， 确定特定代谢因素在触发因素中的实际作用 以及对NV的监管，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， 例如显著扰动(单独或组合) 视网膜氧水平、葡萄糖利用率、乳酸浓度和 视网膜血流，导致周围的生长因子成为 很有效。迄今为止，对数量贡献的直接评价 这些相互依赖的因素一直缺乏，因为它没有 可以执行其中各种代谢信号可以 长期非侵入性评估，跟踪控制 NV的诱导。我们已经开发出多核核磁共振 (核磁共振)技术可以绕过这些技术问题，并且可以 同时记录完整组织的数量贡献 氧水平、葡萄糖利用和乳酸浓度 在同一动物体内NV的发育过程中。 我们建议将这些新开发的核磁共振方法应用于大鼠幼鼠模型 在NV的发病和发展过程中回答以下问题 NV：新陈代谢因素的数量贡献是什么 (视网膜前血氧水平、乳酸浓度、葡萄糖利用率和 视网膜血流)对NV的发展和进展有何影响？我们会 在我们的模型中操作NV的发生，并测量 代谢因素与：a)新城疫的空间位置 视网膜；b)NV的发生和严重程度；c)在 随着时间的推移，NV的发生。这些实验将证明 这些代谢因素的数量贡献以及是否 在这个模型中可以预测NV的发生。