Carotenoids in Vision

类胡萝卜素对视力的影响

• 批准号: 10408671
• 负责人: Johannes Friedrich von Lintig
• 金额: $ 41.49万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10408671
• 关键词: Address; Anatomy; Animal Model; Biochemistry; Biological Assay; Biology; Carotenoids; Catabolism; Cell Death; Chemicals; Chemistry; Cone; Data; Dietary Fats; Dioxygenases; Disease; Enzymes; Equilibrium; Event; Eye; Fostering; Funding; Genetic; Genotype; Health; Human; Inherited; Isomerism; Knockout Mice; Knowledge; Laboratories; Light; Lighting; Lutein; Mediating; Metabolism; Methodology; Mitochondria; Monoclonal Antibodies; Morphology; Mus; Ophthalmology; Oxidative Stress; Oxides; Pathology; Pattern; Photons; Photoreceptors; Physiology; Pigments; Play; Positioning Attribute; Process; Reaction; Reagent; Research; Research Design; Retina; Retinal Pigments; Retinaldehyde; Retinoids; Rhodopsin; Role; Side; Structure of retinal pigment epithelium; Testing; Therapeutic Intervention; Time; Vertebrates; Vision; Vitamin A; adduct; chemical property; chromophore; fight against; innovation; interest; macula; mitochondrial dysfunction; mouse model; neuroprotection; novel; physical property; prevent; retinal damage; stressor; tool; vision science; visual cycle; visual process; zeaxanthin

ABSTRACT Carotenoids, a class of dietary lipids, play critical roles in vision as precursors of retinoids (vitamin A and its metabolites) and macular pigments. Emerging evidence suggests a beneficial interaction between carotenoids and retinoids in the retina. Carotenoids may prevent retinoids to undergo blue light triggered photochemical reactions that eventually can harm the photoreceptors and the adjacent retina pigment epithelium. However, our knowledge about this process is limited and meaningful progress in this research field has been hampered by a lack of suitable animal models. In recent years, our laboratory has established novel tools and reagents that allow us to address three innovative aims. In Aim 1, we will follow the hypothesis that blue light-dependent photo-isomerization of all-trans-retinal can trigger a cascade of events that eventually damage the photoreceptors. We will study the biochemistry of these reactions in the mouse retina and analyze whether chemical scavenging of retinaldehyde can prevent this pathology. For Aim 2, we have established a mouse model that accumulates lutein and zeaxanthin in the retina. The retina of these mice will allow testing of the protective role of carotenoids against light-induced retinal damage and oxidative stress in a small animal model with striking similarity to humans in anatomy, physiology, and genetics. In Aim 3, we will study the involvement of the carotenoid cleavage dioxygenase BCO2 in the metabolism of bisretinoids and oxidized carotenoids. These compounds form as side products of the visual process and can harm photoreceptors and the adjacent retinal pigment epithelium. We will study the biochemistry of the reaction and test whether BCO2 is a modulator of disease states that are characterized by the accumulation of bisretinoids. Understanding the chemistry and biology of carotenoids in vision is of substantial research interest because of the beneficial roles of these pigments for ocular health.

摘要 类胡萝卜素是一类膳食脂质，作为类维生素A（维生素A及其代谢产物）的前体在视觉中起着关键作用。 代谢物）和黄斑色素。新出现的证据表明，类胡萝卜素之间的有益相互作用 和类维生素A。类胡萝卜素可阻止类维生素A发生蓝光引发的光化学反应 这些反应最终会损害光感受器和邻近的视网膜色素上皮。然而，在这方面， 我们对这一过程的了解是有限的，这一研究领域的有意义的进展受到了阻碍 缺乏合适的动物模型。近年来，我们的实验室建立了新的工具和试剂， 这使我们能够实现三个创新目标。 在目标1中，我们将遵循这样的假设，即全反式-视黄醛的蓝光依赖性光异构化可以 引发一系列事件最终破坏光感受器我们将研究这些的生物化学 小鼠视网膜中的反应，并分析是否化学清除视黄醇可以防止这种反应 病理对于目标2，我们已经建立了一种小鼠模型，其在卵巢中积累叶黄素和玉米黄质。 视网膜。这些小鼠的视网膜将允许测试类胡萝卜素对光诱导的视网膜损伤的保护作用。 在解剖学上与人类惊人相似的小动物模型中， 生理学和遗传学。在目标3中，我们将研究类胡萝卜素裂解双加氧酶的参与， BCO2在双维甲酸和氧化类胡萝卜素代谢中的作用。这些化合物作为以下物质的副产物形成： 视觉过程，并可损害光感受器和邻近的视网膜色素上皮。我们会研究 反应的生物化学，并测试BCO2是否是疾病状态的调节剂，其特征在于 双维甲酸的积累。了解视觉中类胡萝卜素的化学和生物学， 由于这些色素对眼睛健康的有益作用，引起了大量的研究兴趣。