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用于研究视网膜代谢的基因编码代谢传感器

Genetically Encoded Metabolic Sensors to Study Retina Metabolism.

作者信息

Wögenstein Gabriele M, Grimm Christian

机构信息

Department of Ophthalmology, Laboratory for Retinal Cell Biology, University Hospital Zurich, University of Zurich, Schlieren, Switzerland.

出版信息

Adv Exp Med Biol. 2025;1468:465-469. doi: 10.1007/978-3-031-76550-6_76.

DOI:10.1007/978-3-031-76550-6_76
PMID:39930239
Abstract

Dysfunctional retinal metabolism has been shown to contribute to retinal diseases such as age-related macular degeneration (AMD), diabetic retinopathy (DR) and inherited retinal degeneration (IRD). Data indicates that metabolism in the retina is complex and involves intricate interactions between cell types, including the exchange of metabolites between photoreceptors and retinal pigment epithelium (RPE) cells. To understand these interactions on a single cell level, cell-type specific expression of genetically encoded metabolic sensors can be used to reach a spatial and temporal resolution that is superior to other techniques. These sensors comprise a metabolite binding site and a fluorescent reporter protein. The binding of the metabolite leads to changes in the emission of the fluorophore which can be detected by specialized microscopy. The usage of such sensors together with other techniques in the normal and diseased retina will not only help to resolve metabolic interactions between cells and fluxes of metabolites but also enhance our understanding of pathophysiological changes in the retina.

摘要

功能失调的视网膜代谢已被证明会导致视网膜疾病,如年龄相关性黄斑变性(AMD)、糖尿病性视网膜病变(DR)和遗传性视网膜变性(IRD)。数据表明,视网膜中的代谢是复杂的,涉及细胞类型之间的复杂相互作用,包括光感受器和视网膜色素上皮(RPE)细胞之间的代谢物交换。为了在单细胞水平上理解这些相互作用,可以使用基因编码代谢传感器的细胞类型特异性表达来达到优于其他技术的空间和时间分辨率。这些传感器包括一个代谢物结合位点和一个荧光报告蛋白。代谢物的结合会导致荧光团发射的变化,这可以通过专门的显微镜检测到。在正常和患病视网膜中使用此类传感器以及其他技术,不仅有助于解析细胞之间的代谢相互作用和代谢物通量,还能增强我们对视网膜病理生理变化的理解。

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本文引用的文献

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Functional principles of genetically encoded fluorescent biosensors for metabolism and their quantitative use.用于代谢的基因编码荧光生物传感器的功能原理及其定量应用。
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Deficits in mitochondrial TCA cycle and OXPHOS precede rod photoreceptor degeneration during chronic HIF activation.慢性 HIF 激活过程中,线粒体三羧酸循环和 OXPHOS 缺陷先于杆状光感受器变性。
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