Transport Processes in Photoreceptors

光感受器中的运输过程

• 批准号: 7768405
• 负责人: YIANNIS KOUTALOS
• 金额: $ 32.52万
• 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 2013-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7768405
• 关键词: Age related macular degeneration; All-Trans-Retinol; Biochemical; Biological Assay; Blindness; Cattle; Cell Death; Complete Blindness; Dark Adaptation; Defect; Detection; Development; Diabetes Mellitus; Disease; Environmental Risk Factor; Excision; Fluorescence; Funding; Goals; Health; High Pressure Liquid Chromatography; Hydrolysis; Lead; Life; Light; Lipid Peroxidation; Macular degeneration; Measures; Membrane; Metabolic; Metabolic Diseases; Microscopy; Mus; Night Blindness; Pathway interactions; Photoreceptors; Photosensitizing Agents; Play; Process; Proteins; Rana; Research; Retina; Retinal; Retinal Diseases; Retinal Pigments; Retinitis Pigmentosa; Retinoids; Retinol Binding Proteins; Retinol dehydrogenase; Rhodopsin; Risk Factors; Role; Serum Albumin; Stargardt' s disease; Structure of retinal pigment epithelium; Sunlight; Time; Toxic effect; Transport Process; chromophore; cytotoxic; cytotoxicity; early onset; extracellular; fluorescence imaging; human disease; improved; insight; instrument; mouse model; oxidation; oxidative damage; prevent; public health relevance; retinal damage; retinal rods; two-photon; visual process; visual processing

DESCRIPTION (provided by applicant): All-trans retinal is generated in photoreceptors as a result of the detection of light by the visual pigment. All-trans retinal is a cytotoxic substance that can initiate oxidative damage and is normally removed rapidly from the photoreceptor. Progress in the previous funding period showed that efficient clearance of all-trans retinal requires metabolic energy and the proper functioning of retinoid processing pathways. The long-term goal of this project is to determine the intracellular, extracellular, and environmental factors that influence clearance of all-trans retinal and protect photoreceptors from its toxicity. The accumulation of all-trans retinal and the resultant oxidative damage will be investigated in isolated photoreceptor membranes, and in living frog and mouse photoreceptors. To carry out these studies, we will combine biochemical assays of all-trans retinal and oxidative damage with fluorescence imaging and oxidation of single photoreceptors using one- and two-photon microscopy. The aims of the proposed research are to: 1. Determine whether the buildup of all-trans retinal promotes oxidative damage. 2. Determine whether improved removal of all-trans retinal prevents oxidative damage. Defects in all-trans retinal removal have been implicated in a variety of retinal diseases, ranging from impaired dark adaptation to complete blindness. The cytotoxicity of all-trans retinal could be a factor in a broad spectrum of pathological conditions, including Age-Related Macular Degeneration, the leading cause of blindness in the US, metabolic diseases like diabetes, and damage to the retina inflicted by sunlight or by ophthalmic instruments. Impaired removal of all-trans retinal may play a role in Stargardt's disease, an early onset form of macular degeneration, and Oguchi's disease, a form of stationary night blindness. The proposed research will determine the basic parameters underlying the photo-oxidative potential of all- trans retinal in photoreceptors. It will determine the metabolic limits at which the clearance of all-trans retinal becomes compromised and allow an assessment of the impact of metabolic perturbations on the long-term health of photoreceptors. It will clarify the role of potential risk factors for the development of Age-Related Macular Degeneration, and elucidate the relation between metabolic limitations, light exposure, and disruptions in retinal processing in Stargardt's and Oguchi's diseases. PUBLIC HEALTH RELEVANCE: All-trans retinal is continuously generated in photoreceptors as a result of the detection of light by the visual pigment. All-trans retinal is a cytotoxic substance that has been implicated in a variety of diseases of the retina, including Age-Related Macular Degeneration, Stargardt's, and some forms of Retinitis Pigmentosa. The long-term goal of this project is to determine the intracellular, extracellular, and environmental factors that influence clearance of all-trans retinal and protect photoreceptors from its toxicity.

描述（由申请人提供）：由于视觉颜料检测光，因此在光感受器中产生了全反式视网膜。全反式视网膜是一种可引发氧化损伤的细胞毒性物质，通常从感光器中迅速去除。在上一个融资期间的进展表明，全跨性别视网膜的有效清除需要代谢能量和视网膜类似加工途径的正常功能。该项目的长期目标是确定影响全反式视网膜清除并保护感光体免受毒性的细胞内，细胞外和环境因素。全反式视网膜的积累和所得的氧化损伤将在孤立的感光膜以及活的青蛙和小鼠光感受器中研究。为了进行这些研究，我们将使用一单光感受器和两光子显微镜结合全反式视网膜和氧化损伤的生化测定和荧光成像和氧化。拟议的研究的目的是：1。确定全反式视网膜的积累是否促进氧化损害。 2。确定改善全反式视网膜的去除是否可以防止氧化损伤。全反式视网膜清除的缺陷已与多种视网膜疾病有关，范围从黑暗适应受损到完全失明。全反式视网膜的细胞毒性可能是广泛的病理状况的一个因素，包括与年龄有关的黄斑变性，美国失明的主要原因，如糖尿病等代谢疾病，以及对阳光或阳光造成的视网膜损害。去除全频道视网膜的障碍可能在Stargardt疾病（黄斑变性的早期发作形式）和Oguchi病（一种固定的夜间失明形式）中发挥作用。拟议的研究将确定光感受器中全反视网膜的光氧化潜力的基本参数。它将确定全变型视网膜清除受到损害的代谢极限，并允许评估代谢扰动对光感受器长期健康的影响。它将阐明潜在危险因素在与年龄相关的黄斑变性发展中的作用，并阐明Stargardt和Oguchi疾病中的代谢局限性，光暴露和视网膜处理中的破坏之间的关系。公共卫生相关性：视觉颜料检测到光的结果，全型视网膜是在光感受器中连续产生的。全反式视网膜是一种细胞毒性物质，与视网膜的多种疾病有关，包括与年龄相关的黄斑变性，Stargardt和某些形式的色素性视网膜炎。该项目的长期目标是确定影响全反式视网膜清除并保护感光体免受毒性的细胞内，细胞外和环境因素。