Microenvironment of the retina

描述（由申请人提供）：这项工作的长期目标是了解与氧和pH有关的视网膜微环境的各个方面，以及这些与哺乳动物视网膜体内能量代谢和功能的关系。虽然这项工作将在动物身上进行，但它与影响人类循环和视网膜神经元之间关系的致盲疾病特别相关。在下一个项目期间，我们的主要研究方向是糖尿病视网膜病变、视网膜脱离和视网膜动脉闭塞性疾病。然而，该结果也将提供可能与其他类型的视网膜功能障碍相关的基本信息。这项拟议的工作将主要在完整的麻醉猫身上进行，因为它们的视网膜为人类视网膜提供了一个很好的模型。这项技术主要是使用氧气和pH值敏感的微电极来绘制视网膜氧气水平、pH值和电活动（视网膜电图），具有高空间和时间分辨率，就像我们之前在其他实验条件下所做的那样。在测量之后，将使用扩散的数学建模来提取仅从测量中不明显的代谢参数，并对可能无法进行实验的情况进行模拟。还将进行一些视网膜组织学测量。该项目有5个具体目标。1)我们将研究光凝后的视网膜内氧合，因为光凝阻碍新生血管形成的机制尚不清楚。2)我们将利用特异目的1中光凝后氧合的信息，建立适当的二维扩散模型，希望为设计治疗视网膜病变的病变密度和大小提供更好的理论依据。3)我们将研究脱离视网膜的视网膜氧合，以了解高氧对视网膜脱离的保护作用的基础，这是最近在猫身上发现的。4)我们将研究视网膜动脉闭塞后的pH值，了解酸中毒对视网膜损伤的潜在作用。5)我们将研究麻醉对我们所做的代谢测量的影响，并将研究猫和灵长类动物视网膜之间的代谢差异。

DESCRIPTION (provided by applicant): The long-term objectives of this work are to understand aspects of the retinal microenvironment related to oxygen and pH, and how these relate to energy metabolism and function of the mammalian retina in vivo. While this work will be done in animals, it is particularly relevant to blinding diseases that affect the relationships between the circulation and retinal neurons in humans. During the next project period, our main interests are in diabetic retinopathy, retinal detachment, and retinal arterial occlusive disease. However, the results will also provide fundamental information that may be relevant to other types of retinal dysfunction. The proposed work will be done primarily on intact anesthetized cats, since their retina provides a good model for much of the human retina. The techniques are primarily to use oxygen and pH sensitive microelectrodes to map out retinal oxygen levels, pH and electrical activity (the electroretinogram) with high spatial and temporal resolution, as we have done previously under other experimental conditions. Following the measurements, mathematical modeling of diffusion will be used to extract metabolic parameters that are not apparent from the measurements alone, and to perform simulations of situations that may not be amenable to experimentation. Some measurements of retinal histology will also be made. The project has 5 specific aims. 1) We will study intraretinal oxygenation following photocoagulation, because the mechanism by which photocoagulation blocks neovascularization is still unclear. 2) We will use information about oxygenation after photocoagulation from specific aim 1 to create an appropriate two-dimensional diffusion model of this situation, with the hope of providing a better rationale for the density and size of lesions designed to treat retinopathy. 3) We will study retinal oxygenation in the detached retina in order to understand the basis for the protective effect of hyperoxia in retinal detachment, which has been shown recently in cats. 4) We will study pH after retinal arterial occlusion, to understand the potential role of acidosis in damaging the retina. 5) We will investigate the influence of anesthesia on the metabolic measurements we make, and will study metabolic differences between the cat and primate retinas.