Control of Photoreceptor Metabolism

项目总结/摘要 对光感受器的代谢需求的一般理解可以导致广泛的 适用的治疗策略，以治疗由不同的遗传和 环境因素考虑到这一点，我们一直在研究 视网膜和视网膜色素上皮（RPE）中能量代谢的性质。 光感受器代谢受来自RPE的营养物质的可用性限制。 有证据表明，视网膜和RPE作为一个网络共同起作用， 代谢特化和相互依赖的细胞。我们假设， 该网络的任何组成部分都可能导致视网膜变性， 整个代谢生态系统。我们最近的研究结果支持这一假设。我们有 提出了一个模型，其中葡萄糖从脉络膜血液通过RPE的流动 通过光感受器中的糖酵解产生的乳酸盐来增强对视网膜的吸收。乳酸 不仅为RPE细胞提供能量，而且影响RPE细胞的分化状态。 这些意见是本建议具体目标的基础。第一个目标将 探索增强葡萄糖通过视网膜色素上皮流动的方法。第二个目标将 研究乳酸盐如何影响RPE细胞的分化。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 用于设计治疗方法，使眼睛中的光感受器更强大， 对遗传和环境因素有抵抗力， 光感受器变性 .

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. .