Retinoids in Vision

当光子进入眼睛时，视网膜通过一种电子信号将它们转换成电信号。 称为光转导的生化过程。然后，这个信号被传递到大脑的视觉皮质， 视觉感知发生的地方。视觉系统允许我们在一生中不断地感知光线 因为它有再生蛋白质和光敏发色团的能力。长期目标 建议的研究之一是了解11顺式视网膜的再生，11顺式视网膜是视网膜中普遍存在的生色团。 脊椎动物视网膜。11-顺式视黄醇与视杆细胞和视锥细胞中的视蛋白偶联 在光的作用下被光异构化为全反式视网膜。失活和再生的重要性 光激活的视紫红质最近变得明显，因为在处理这一过程中出现了故障 发色团和视紫红质再生的抑制会导致视力受损和视神经变性 光感受器。阐明维甲酸循环中涉及的分子步骤将极大地有助于 我们对这些疾病状态的基础的理解，并为发展 治疗人类视觉疾病的合理方法。 我们建议研究视觉循环中的四个基本步骤，以及每个步骤是如何涉及 光传导猝灭与视紫红质的再生。我们想要(1)调查这个角色 光感受器脱氢酶在光转导和类维A酸循环中的作用，包括RDH12的作用 和PrRdH及其底物全反式，暗适应；(2)异构化的纯化和鉴定 复合体；(3)提纯和表征视网膜小体，视觉周期的酯存储颗粒；表征 缺乏视网膜小体支柱蛋白之一的ADRP的小鼠的这些结构；以及(4)LRAT的特征 结构、功能和生理水平上的酶。本申请中建议的研究将添加 维甲酸循环中尚不清楚的步骤的新的生化和生理信息 但它们对光感受器的正常功能至关重要。

When photons of light enter the eye, the retina converts them into an electrical signal through a biochemical process called phototransduction. This signal is then relayed to the visual cortex of the brain, where visual perception occurs. The visual system allows us to continually perceive light throughout our lives because it has the ability to regenerate proteins and the light-sensitive chromophore. The long-term objective of the proposed studies is to understand the regeneration of 11-cis-retinal, the universal chromophore of the vertebrate retina. 11-cis-Retinal is coupled to the protein opsin in both rod and cone photoreceptor cells and is photoisomerized to all-trans-retinal by light. The importance of the inactivation and regeneration of photoactivated rhodopsin has become apparent recently, as malfunctions in the processing of this chromophore and the inhibition of rhodopsin regeneration lead to impairment of vision and to degeneration of photoreceptors. Elucidation of the molecular steps involved in the retinoid cycle would greatly contribute to our understanding of the basis of these disease states and provide a foundation for the development of rational approaches to the treatment of human visual diseases. We propose to examine four fundamental steps in the visual cycle and how each step is involved in the quenching of phototransduction and the regeneration of rhodopsin. We would like to (1) investigate the role of photoreceptor dehydrogenases in phototransduction and the retinoid cycle, including the role of RDH12 and prRDH, and its substrate, all-trans-RAL, in dark adaptation; (2) purify and characterize the isomerization complex; (3) purify and characterize retinosomes, the ester storage particles of the visual cycle; characterize these structures in mice lacking ADRP, one of the pillar proteins of retinosomes; and (4) characterize LRAT enzymes on the structural, functional, and physiological level. Studies proposed in this application will add new biochemical and physiological information to steps in the retinoid cycle that are as yet poorly understood but which are critical for the normal function of photoreceptors.