Retinoids in Vision

当光的光子进入眼睛时，视网膜通过视网膜将它们转换成电信号。 生化过程称为光转导。然后这个信号被传递到大脑的视觉皮层， 视觉感知发生的地方。视觉系统使我们能够在一生中不断感知光 因为它具有再生蛋白质和光敏发色团的能力。长期目标 拟议研究的目的是了解 11-顺式视黄醛的再生，这是生物体的通用生色团 脊椎动物的视网膜。 11-cis-Retinal 与视杆细胞和视锥细胞感光细胞中的蛋白视蛋白偶联， 被光光异构化为全反式视网膜。失活和再生的重要性 光激活视紫红质最近变得明显，因为这种处理过程中出现故障 发色团和视紫红质再生的抑制会导致视力受损和视神经退化 光感受器。阐明类维生素A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基础的理解并为发展提供了基础 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如何参与视觉循环 光转导的猝灭和视紫红质的再生。我们想（1）调查这个角色 光感受器脱氢酶在光转导和类视黄醇循环中的作用，包括 RDH12 的作用 和 prRDH 及其底物全反式 RAL，处于暗适应状态； (2) 异构化的纯化和表征 复杂； (3) 纯化和表征视黄体，即视觉循环的酯存储颗粒；表征 缺乏ADRP（视网膜体的支柱蛋白之一）的小鼠体内的这些结构； (4) 表征 LRAT 结构、功能和生理水平上的酶。本申请中提出的研究将添加 关于类视黄醇循环步骤的新生化和生理信息，目前尚知之甚少 但这对于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.