A clinically applicable model of retinal oxygen metabolism

项目摘要 该建议旨在建立视网膜内层的代谢与氧之间的相关性。 通过光学相干断层扫描测量来自视网膜内血管网的供应。这项工作将 在大鼠中完成，但将立即进行临床应用。几种重要的疾病会损害人的内在 视网膜，包括糖尿病、青光眼和血管闭塞。在测量方面， 提供关于内部视网膜的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），但每一个单独的是不足以让强有力的结论。 现在，在动物和人类中，将饱和度和血流一起测量并联合收割机 它们产生氧的内部视网膜代谢率（IR-MRO 2），其是氧的总量 每单位时间从视网膜循环中提取。这些IR-MRO 2的非侵入性测量可以 可能在其他措施之前预测疾病中的功能损伤，并且可能在 评估这些疾病的治疗方法。测量IR-MRO 2的最有前途的方法是使用 可见光光学相干断层扫描（vis-OCT）。然而，视网膜是一种独特的组织， 因此需要进一步验证，以了解IR-MRO 2如何对应于实际氧气利用率 视网膜内层（IR-QO 2）。人们经常假设这两个量相等，但事实并非如此。那里 是视网膜循环提供视网膜所需氧气的重要成分的条件。 光感受器在外层视网膜，所以IR-MRO 2高估IR-QO 2，和其他条件下，氧 来自脉络膜的氧向内层视网膜提供氧，因此IR-MRO 2低估了IR-QO 2。如果 IR-MRO 2和IR-QO 2之间的实际对应关系尚不清楚，新方法的巨大前景 由于混淆和错误的结论，测量IR-MRO 2的可能性将丢失。实际上， 了解糖尿病、青光眼和静脉阻塞时视网膜内部变化的进展。我们提出 用两种成熟的氧敏微电极方法对同一大鼠进行实验 和vis-OCT，以确定IR-MRO 2可用于直接推断IR-QO 2的条件，并提供 一种临床上有用的模型，可以预测IR-MRO 2和IR-QO 2之间的偏差。没有研究 先前在同一动物中使用成像和微电极，或试图提供 血氧测定法与其他方法。所提出的工作是重要的任何方法表征IR- 具体目标是：1）开发一个分析模型，将视网膜内sO2与视网膜内动脉血氧饱和度（sO2） 和IR-MRO 2，通过vis-OCT测量，对大鼠和大鼠的内视网膜和外视网膜的代谢需求， 2）通过几乎同时测量IR-MRO 2和 从微电极测量在光和暗下呼吸空气期间得出的氧消耗， 缺氧和高氧。

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.