Microenvironment of the retina

描述(申请人提供)：这项工作的长期目标是了解视网膜微环境与氧气和pH有关的方面，以及这些因素如何与活体中哺乳动物视网膜的能量代谢和功能有关。虽然这项工作将在动物身上完成，但它与影响人类血液循环和视网膜神经元之间关系的致盲疾病特别相关。在接下来的项目期间，我们的主要兴趣是糖尿病视网膜病变、视网膜脱离和视网膜动脉闭塞疾病。然而，这些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。拟议的工作将主要在完整的麻醉猫身上完成，因为它们的视网膜为人类视网膜的大部分提供了一个很好的模型。这些技术主要是使用氧和pH敏感的微电极来绘制高空间和时间分辨率的视网膜氧水平、pH和电活动(视网膜电信号)，就像我们以前在其他实验条件下所做的那样。在测量之后，将使用扩散的数学模型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。还将进行视网膜组织学的一些测量。该项目有5个具体目标。1)我们将研究光凝后视网膜内的氧合作用，因为光凝阻止新生血管的机制尚不清楚。2)我们将使用特定目标1中关于光凝后氧合的信息来创建适合这种情况的二维扩散模型，以期为设计用于治疗视网膜病变的病变的密度和大小提供更好的理论基础。3)我们将研究视网膜脱离中的视网膜氧合作用，以了解高氧在视网膜脱离中保护作用的基础，这是最近在猫身上发现的。4)我们将研究视网膜动脉阻塞后的pH值，以了解酸中毒在视网膜损伤中的潜在作用。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.