Control of Photoreceptor Metabolism

项目摘要/摘要 对光感受器的新陈代谢需求的一般理解可以导致广泛的 治疗由不同基因和基因引起的视网膜压力的适用治疗策略 环境因素。考虑到这一点，我们一直在调查 视网膜和视网膜色素上皮(RPE)能量代谢的本质。 光感受器的新陈代谢受到RPE中营养物质供应的限制。 有证据表明，视网膜和RPE作为一个网络共同发挥作用 代谢专门化和相互依赖的细胞。我们假设……的一个缺陷 该网络的任何组成部分都可能导致视网膜退化，这是 整个新陈代谢生态系统。我们最近的发现支持了这一假设。我们有 提出了一个模型，在该模型中，来自脉络膜血液的葡萄糖通过RPE流动 光感受器中糖酵解产生的乳酸增强了对视网膜的敏感性。乳酸盐 它不仅为RPE提供燃料，而且还能影响RPE细胞的分化状态。 这些意见是本提案具体目标的基础。第一个目标是 探索增强跨RPE的葡萄糖流动的方法。第二个目标是 研究乳酸对RPE细胞分化的影响。该项目将确定 增强葡萄糖通过RPE流向视网膜的方法。我们的发现可以是 用于设计治疗方法，使眼睛的光感受器更健壮 对遗传和环境因素具有抵抗力，这些因素通常会导致 光感受器退化。 。

Project Summary/Abstract A general understanding of the metabolic needs of photoreceptors could lead to broadly applicable therapeutic strategies to treat retinas stressed by diverse genetic and environmental factors. With that in mind, we have been investigating the fundamental nature of energy metabolism in the retina and the retinal pigment epithelium (RPE). Photoreceptor metabolism is limited by the availability of nutrients from the RPE. Evidence indicates that the retina and RPE function together as a network of metabolically specialized and interdependent cells. We hypothesize that a deficiency in any component of that network could lead to retinal degeneration as part of the failure of the entire metabolic ecosystem. Our recent findings support this hypothesis. We have proposed a model in which the flow of glucose from the choroidal blood through the RPE to the retina is enhanced by lactate produced by glycolysis in photoreceptors. Lactate not only fuels the RPE, but it also can influence the differentiation state of RPE cells. These observations are the basis for the specific aims of this proposal. The first aim will explore ways to enhance the flow of glucose across the RPE. The second aim will investigate how lactate influences differentiation of RPE cells. This project will identify ways to enhance the flow of glucose across the RPE to the retina. Our findings can be used to design therapeutic approaches that make photoreceptors in an eye more robust and resistant to genetic and environmental factors that normally would cause photoreceptor degeneration. .