Carotenoids in Vision

摘要 类胡萝卜素是一类饮食脂质，作为维甲酸(维生素A和维生素A)的前体，在视觉中起着至关重要的作用。 代谢物)和黄斑色素。新出现的证据表明，类胡萝卜素之间存在有益的相互作用 和视网膜中的维甲酸。类胡萝卜素可能会阻止维甲酸经历蓝光引发的光化学 最终会损害光感受器和邻近的视网膜色素上皮的反应。然而， 我们对这一过程的了解有限，在这一研究领域取得的有意义的进展受到了阻碍 由于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，我们将遵循蓝光依赖的全反式视网膜光异构化可以 引发一系列事件，最终损害光感受器。我们将研究这些生物的生物化学 在小鼠视网膜中的反应，并分析化学清除视黄醛是否可以阻止这种反应 病理学。对于目标2，我们建立了一种小鼠模型，在体内积累了叶黄素和玉米黄质 视网膜。这些小鼠的视网膜将可以测试类胡萝卜素对光诱导的保护作用 一种在解剖学上与人类惊人相似的小动物模型的视网膜损伤和氧化应激， 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A酸和氧化类胡萝卜素代谢中的作用。这些化合物作为副产品形成 并且会损害光感受器和邻近的视网膜色素上皮。我们会研究 反应的生物化学和测试BCO2是否是疾病状态的调节器，其特征是 双维A酸类化合物的积累。在视觉上理解类胡萝卜素的化学和生物学是 由于这些色素对眼睛健康的有益作用，人们对此有很大的研究兴趣。

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.