A clinically applicable model of retinal oxygen metabolism

临床适用的视网膜氧代谢模型

• 批准号: 9227475
• 负责人: ROBERT A. LINSENMEIER
• 金额: $ 19.56万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-02-01 至 2019-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9227475
• 关键词: Adopted; Air; Anatomy; Animals; Blood Circulation; Blood Vessels; Blood flow; Breathing; Cerebrum; Choroid; Clinical; Confusion; Darkness; Diabetes Mellitus; Disease; Disease Progression; Glaucoma; Goals; Hospitals; Human; Hyperoxia; Hypoxia; Image; Intervention; Light; Light Coagulation; Measurement; Measures; Metabolic; Metabolism; Methods; Microelectrodes; Modeling; Names; National Eye Institute; Optical Coherence Tomography; Oxygen; Oxygen Consumption; Oxygen saturation measurement; Photoreceptors; Protocols documentation; Rattus; Research; Retina; Retinal; Rodent; Techniques; Technology; Testing; Time; Tissues; Translating; Validation; Vascular blood supply; Visible Radiation; Work; bevacizumab; blood flow measurement; clinical application; experimental study; interest; mathematical analysis; metabolic rate; novel; oxygen microelectrode; predictive modeling; retina blood vessel structure; vein occlusion

Project Summary This proposal seeks to establish a correlation between the metabolism of the inner retina and the oxygen supply from the inner retinal vascular network measured by optical coherence tomography. This work will be done in rats, but will have immediate clinical application. Several important diseases cause damage to the inner retina, including diabetes, glaucoma, and vascular occlusion. Considerable effort has gone into measuring parameters that provide some information about the metabolism of the inner retina, particularly oxygen saturation (sO2) in the retinal vessels and retinal blood flow (RBF), but each alone is insufficient to allow strong conclusions. It has now become possible in animals and humans to measure saturation and blood flow together and combine them to yield the Inner Retinal Metabolic Rate of Oxygen (IR-MRO2), which is the total amount of oxygen extracted from the retinal circulation per unit time. These non-invasive measurements of IR-MRO2 could potentially be predictive of functional damage in disease before other measures, and could be useful in evaluating treatments for those diseases. The most promising way to measure IR-MRO2 is a novel method using visible-light optical coherence tomography (vis-OCT). However, the retina is a unique tissue with a dual blood supply, so further validation is required to understand how IR-MRO2 corresponds to the actual oxygen utilization of the inner retina (IR-QO2). It is often assumed that these two quantities are equal, but this is not true. There are conditions under which the retinal circulation provides an important component of the oxygen needed by the photoreceptors in the outer retina, so IR-MRO2 overestimates IR-QO2, and other conditions under which oxygen derived from the choroid provides oxygen to the inner retina, so that IR-MRO2 underestimates IR-QO2. If the actual correspondence between IR-MRO2 and IR-QO2 is not understood, the great promise of the new methods of measuring IR-MRO2 will be lost due to confusion and false conclusions. It is really IR-QO2 that is needed for understanding the progression of inner retinal changes in diabetes, glaucoma, and vein occlusion. We propose to perform experiments on the same rats with both well-established oxygen-sensitive microelectrode methods and vis-OCT to identify the conditions under which IR-MRO2 can be used to infer IR-QO2 directly, and to provide a clinically useful model to allow a prediction of the deviations between IR-MRO2 and IR-QO2. No study has previously used both imaging and microelectrodes in the same animals, or attempted to provide validation of oximetry methods with other methods. The proposed work is important for any method of characterizing IR- MRO2, not just vis-OCT. The specific aims are 1) to develop an analytical model to relate the inner retinal sO2 and IR-MRO2, measured by vis-OCT, to the metabolic demands of the inner and outer retina in both rats and humans and 2) to validate and refine this model in rats by nearly simultaneous measurement of IR-MRO2 and oxygen consumption derived from microelectrode measurements during air breathing in light and darkness, hypoxia and hyperoxia.

项目摘要 该提议旨在建立内部视网膜的代谢与氧气之间的相关性 通过光学相干断层扫描测量的内部视网膜血管网络的供应。这项工作将是 在大鼠中完成，但会立即进行临床应用。几种重要疾病会损害内部 视网膜，包括糖尿病，青光眼和血管阻塞。衡量的巨大努力 提供有关内部视网膜代谢的一些信息的参数，尤其是氧饱和度 （SO2）在视网膜血管和视网膜血流（RBF）中，但单独的每个人都不足以得出强烈的结论。 现在，动物和人类已经有可能测量饱和度和血流在一起并结合在一起 它们产生氧气内代谢率（IR-MRO2），这是氧气的总量 从单位时间的视网膜循环中提取。这些IR-MRO2的非侵入性测量可能 在其他措施之前可能会预测疾病的功能损害，并且可能有用 评估这些疾病的治疗方法。测量IR-MRO2的最有希望的方法是使用新颖的方法 可见光光学相干断层扫描（VIS-OCT）。但是，视网膜是一种独特的组织，有双血 供应，因此需要进一步验证才能了解IR-MRO2与实际氧气的相对应 内部视网膜（IR-QO2）。通常认为这两个数量是相等的，但这不是事实。那里 是视网膜循环提供的条件 外视网膜中的感光体，因此IR-Mro2高估了IR-QO2，以及其他条件下的氧气 源自脉络膜的源自内部视网膜的氧气，因此IR-MRO2低估了IR-QO2。如果是 IR-MRO2和IR-QO2之间的实际对应关系尚不清楚，这是新方法的巨大希望 由于混乱和错误的结论，测量IR-MRO2的测量将丢失。确实是IR-QO2 了解糖尿病，青光眼和静脉阻塞的视网膜内部变化的进展。我们建议 用两个具有良好氧敏感的微电极方法在同一大鼠上进行实验 并相互确定可以使用IR-MRO2直接推断IR-QO2的条件，并提供 临床上有用的模型，可以预测IR-MRO2和IR-QO2之间的偏差。没有研究 以前在同一动物中同时使用了成像和微电极，或试图提供验证 使用其他方法的血氧仪方法。提出的工作对于表征IR-的任何方法都很重要 MRO2，不仅仅是相关。具体目的是1）开发一个分析模型以关联内部视网膜SO2 通过Vis-OCT测量的IR-MRO2满足了大鼠内部和外视网膜的代谢需求 人类和2）通过几乎同时测量IR-Mro2和 在光和黑暗中空气呼吸期间微电极测量的氧气消耗， 缺氧和高氧。