Retinoids in Vision

当光的光子进入眼睛时，视网膜通过一个微通道将它们转换成电信号。 一个叫做光传导的生化过程。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地感知光线 因为它具有再生蛋白质和光敏发色团的能力。长期目标 提出的研究是了解再生的11-顺式-视网膜，通用的发色团的 脊椎动物视网膜11-顺式-视网膜与视杆和视锥感光细胞中的蛋白质视蛋白偶联， 被光异构化为全反式视黄醛。失活和再生的重要性 光活化视紫红质最近变得明显，因为在这种处理过程中的故障， 发色团和视紫红质再生的抑制导致视力受损和视网膜变性。 光感受器阐明类维生素A循环中涉及的分子步骤将大大有助于 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。 我们建议检查视觉周期中的四个基本步骤，以及每一步如何参与 光传导的淬灭和视紫红质的再生。我们希望（1）研究角色 光转导和类维生素A循环中的光感受器降解酶，包括RDH 12的作用 和prRDH及其底物全反式RAL的异构化;（2）纯化并表征了 复合物;（3）纯化和表征视色素体，视觉循环的酯储存颗粒;表征 这些结构在缺乏ADRP的小鼠中，ADRP是视网膜体的支柱蛋白之一;以及（4）表征LRAT 酶的结构，功能和生理水平。本申请中提出的研究将增加 新的生化和生理信息的步骤，在维甲酸循环，但还不清楚 但是对于光感受器的正常功能是关键的。

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.