A clinically applicable model of retinal oxygen metabolism

项目摘要 这一建议旨在建立视网膜内部新陈代谢和氧气之间的联系。 由光学相干断层扫描测量的视网膜内血管网供血。这项工作将是 在老鼠身上进行，但将立即应用于临床。几种重要的疾病会对心脏造成损害。 视网膜，包括糖尿病、青光眼和血管阻塞。在测量方面已经付出了相当大的努力 提供有关视网膜内部新陈代谢的一些信息的参数，特别是氧饱和度 (SO2)在视网膜血管和视网膜血流(RBF)，但每个单独都不足以得出强有力的结论。 现在，在动物和人类身上一起测量饱和度和血流并结合在一起已经成为可能 以产生视网膜内氧代谢率(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的非侵入性测量可以 在其他措施之前，潜在地预测疾病中的功能损害，并可能在 评估这些疾病的治疗方法。最有希望测量IR-MRO2的方法是一种新的方法，它使用 可见光光学相干层析成像(VIS-OCT)。然而，视网膜是一种独特的组织，具有双重血液 因此，需要进一步验证以了解IR-MRO2如何与实际氧气利用相对应 视网膜内层(IR-QO2)。人们通常认为这两个量相等，但事实并非如此。那里 是指视网膜循环提供人体所需氧气的重要成分。 视网膜外部的光感受器，所以IR-MRO2高估了IR-QO2，以及其他条件下氧气 来自脉络膜的氧气为视网膜内部提供氧气，因此IR-MRO2低估了IR-QO2。如果 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 由于混淆和错误的结论，IR-MRO2的测量结果将会丢失。真正需要IR-QO2的是 了解糖尿病、青光眼和静脉阻塞时视网膜内部变化的进展情况。我们建议 用两种成熟的氧敏感微电极方法在同一只大鼠身上进行实验 和VIS-OCT，以确定IR-MRO2可用于直接推断IR-QO2的条件，并提供 一个临床上有用的模型，可以预测IR-MRO2和IR-QO2之间的偏差。没有一项研究 以前在同一动物中同时使用成像电极和微电极，或试图提供对 血氧测定法与其他方法相结合。所提出的工作对于任何表征IR的方法都是重要的。 MRO2，而不仅仅是VS-OCT。具体目标是1)开发一个分析模型来关联视网膜内部的SO2 和IR-MRO2，通过VIS-OCT测量，对大鼠和大鼠视网膜内外的代谢需求 人和2)通过几乎同时测量IR-MRO2和 在白天和黑暗中呼吸空气时，通过微电极测量得出的氧气消耗量， 低氧和高氧。

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.