Transport processes in photoreceptors

光感受器中的运输过程

• 批准号: 6821952
• 负责人: YIANNIS KOUTALOS
• 金额: $ 28.64万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-06 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6821952
• 关键词: Rana; carotenoids; cell surface receptors; charge coupled device camera; chemical kinetics; chromophore; enzyme activity; eye; fluorescence recovery after photobleaching; genetically modified animals; hydrolysis; laboratory mouse; oxidoreductase; photon absorptiometry; protein transport; retinal pigment epithelium; retinaldehyde; rhodopsin; rod cell; visual photoreceptor

DESCRIPTION (provided by applicant): Light activation of the vertebrate rod photoreceptor visual pigment rhodopsin requires the isomerization of the chromophore 11-cis retinal to the all-trans form. The regeneration of photosensitive rhodopsin containing 11-cis retinal is achieved through a series of reactions in the photoreceptors and retinal pigment epithelium. In photoreceptors, these steps include the hydrolysis of the protein-chromophore bond generating all-trans retinal, its subsequent reduction by retinol dehydrogenase to all-trans retinol, and removal of all-trans for further processing. Defects in these photoreceptor pathways have deleterious consequences for photoreceptor health and function. The long-term goal of this project is to understand the normal kinetic properties of these pathways and how specific mutations influence retinal processing. The kinetics of all-trans retinol formation and removal will be investigated in lower vertebrate and mouse photoreceptor preparations. As all-trans retinol is fluorescent, we will carry out these studies using fluorescence imaging of living photoreceptors with single and two-photon microscopy. The aims of the proposed research are to: (1) Determine the kinetics of all-trans retinol formation and removal in lower vertebrate photoreceptors. (2) Determine the kinetics of all-trans retinol formation in the photoreceptors of the normal mouse and in mouse models of clinical disorders. The regeneration of visual pigment underlies our ability to see continuously and under a wide range of light intensities. Defects in visual pigment regeneration have been implicated in a variety of retinal diseases ranging from impaired dark adaptation to complete blindness. The proposed research will determine which steps control retinoid processing in photoreceptors. It will also provide new information on how retinoid processing is affected in models of Stargardt's disease, an early onset form of macular degeneration, and Oguchi's disease, a form of stationary night blindness.

描述（由申请人提供）：脊椎动物杆光感受器视觉色素的光激活需要将发色团11-cis视网膜的异构化与全反式形式形式。通过感光体和视网膜色素上皮的一系列反应，可以实现含有11张视网膜的光敏感蛋白的再生。在感光细胞中，这些步骤包括产生全反式视网膜的蛋白质 - 肉眼键的水解，随后将视黄醇脱氢酶降低至全反式视黄醇，以及去除全元素以进一步加工。这些光感受器途径中的缺陷对光感受器的健康和功能产生有害后果。该项目的长期目标是了解这些途径的正常动力学特性以及特定突变如何影响视网膜处理。 将在下部脊椎动物和小鼠感光体制剂中研究全型视黄醇形成和去除的动力学。由于全反式视黄醇是荧光的，我们将使用具有单一和两光子显微镜的活体感受器的荧光成像进行这些研究。 拟议研究的目的是： （1）确定下部脊椎动物中全型视黄醇形成和去除的动力学 感受器。 （2）确定正常小鼠的感光体和临床疾病的小鼠模型中的全反式视黄醇形成的动力学。 视觉颜料的再生是我们连续且在各种光强度下看到的能力。视觉色素再生中的缺陷与多种视网膜疾病有关，范围从黑暗适应受损到完全失明。拟议的研究将确定哪些步骤控制感光体中的类视黄素处理。它还将提供有关类视黄度加工在Stargardt疾病模型，黄斑变性的早期发作和Oguchi氏病的新信息，这是一种固定的夜间失明。