Assessing Photoreceptor Structure and Function in Normal and Diseased Retina

评估正常和患病视网膜的感光器结构和功能

• 批准号: 7854554
• 负责人: Joseph Carroll
• 金额: $ 1.37万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-15 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7854554
• 关键词: Address; Affect; Appearance; Biological; Biological Process; Biomedical Engineering; Cancer Center Support Grant; Cell physiology; Cellular biology; Clinical; Color vision defect; Complement; Complex; Contrast Sensitivity; Densitometry; Development; Disease; Disease Progression; Electrophysiology (science); Environment; Foundations; Functional Magnetic Resonance Imaging; Future; Genes; Genetic Techniques; Grant; Human; Image; Imaging Techniques; Individual; Inherited; Link; Missense Mutation; Molecular Genetics; Mutation; Nature; Neurobiology; Ophthalmology; Ophthalmoscopy; Opsin; Optical Coherence Tomography; Optics; Photoreceptors; Physiological; Physiological Processes; Pigments; Positioning Attribute; Postdoctoral Fellow; Psychophysics; Psychophysiology; Research; Resolution; Retina; Retinal; Retinal Cone; Retinal Degeneration; Retinal Diseases; Retinitis Pigmentosa; Structure; Structure-Activity Relationship; Techniques; Technology; Testing; Thinking; Training; Translations; United States National Institutes of Health; Universities; Variant; Vision; Vision Disorders; Visual; Visual system structure; Wisconsin; Work; adaptive optics; design; experience; functional status; genetic analysis; in vivo; insight; interdisciplinary approach; medical schools; mutant; novel; prevent; programs; public health relevance; regional difference; research study; tomography; tool; visual performance

DESCRIPTION (provided by applicant): This proposal addresses 2 of the program objectives of the NEI Retinal Diseases Panel: - "Explore the topographical and regional differences of the retina and the relationship of this topography to disease progression". - "Continue to develop and apply noninvasive technologies such as functional magnetic resonance imaging (fMRI), ocular coherence tomography, adaptive optics, and confocal imaging to better understand retinal function and changes in disease states". The overall purpose of this proposal is to characterize the topography of the cone mosaic in normal and diseased retinae, to examine the factors that might govern this topography, and to assess photoreceptor function in these mosaics. I have discovered novel cone degeneration mechanisms linked to mutations in the cone photopigments. The experiments in this proposal will help clarify the deleterious effects of disruptions in cone pigment expression, both on the appearance of the cone mosaic and on visual performance. This proposal is the first step in an effort to build a research program that will contribute to the understanding of fundamental biological processes underlying cone vision and vision disorders. By examining how topographical disruptions in the cone mosaic affect visual function (contrast sensitivity, acuity, sensitivity), I will gain novel insight into the structure-function relationship on a cellular level. Moreover, the methodological approach developed in this proposal will be translatable to other retinal diseases that are more complex in nature. Through a unique collaborative effort, I propose to combine psychophysical, electrophysiological, and genetic techniques with in vivo imaging techniques (such as optical coherence tomography & adaptive-optics ophthalmoscopy) to address the following aims: Specific Aim 1 - Characterize the S-cone submosaic in normal and tritan subjects and its relationship to the overall topography of the retina. Specific Aim 2 - Examine the effects of mutations in the L/M-photopigment gene array on the viability of the cones and the organization of the photoreceptor mosaic. Specific Aim 3 - Determine the consequences of cone-opsin mutations and disorganization of the cone mosaic for cone and visual system function. PUBLIC HEALTH RELEVANCE: The majority of our visual activity relies on the cone photoreceptors in the retina. This proposal employs a multidisciplinary approach (using high-resolution retinal imaging, genetic analysis, and electrophysiological tests) to investigate how mutations in the cone pigments affect cone-photoreceptor structure & function. The work in this proposal will serve as the foundation for translation of this same approach to the future study of other retinal degenerations, which will accelerate progress for the effective implementation of novel therapies.

描述（由申请人提供）：该提案解决了NEI视网膜疾病面板的计划2：“探索视网膜的地形和区域差异以及该地形与疾病进展的关系”。 - “继续开发和应用无创技术，例如功能磁共振成像（fMRI），眼相干性断层扫描，适应性光学和共聚焦成像，以更好地了解视网膜功能和疾病状态的变化”。该提案的总体目的是表征正常和患病视网膜中锥体马赛克的地形，以检查可能控制该地形的因素，并评估这些镶嵌物中的光感受器功能。我发现了与锥光片中突变有关的新型锥变性机制。该提案中的实验将有助于阐明锥色表达中破坏的有害影响，包括锥体镶嵌和视觉性能。该提案是建立研究计划的第一步，该计划将有助于理解锥形视力和视力障碍的基本生物学过程。通过检查锥体镶嵌物中的地形破坏如何影响视觉功能（对比灵敏度，敏锐度，灵敏度），我将在细胞水平上对结构功能关系的新见解。此外，本提案中开发的方法论方法将可以翻译成本质上更复杂的其他视网膜疾病。 Through a unique collaborative effort, I propose to combine psychophysical, electrophysiological, and genetic techniques with in vivo imaging techniques (such as optical coherence tomography & adaptive-optics ophthalmoscopy) to address the following aims: Specific Aim 1 - Characterize the S-cone submosaic in normal and tritan subjects and its relationship to the overall topography of the retina.具体目标2-检查突变在L/M photopigment基因阵列中对锥体的可行性和感光体镶嵌的组织的影响。具体目标3-确定锥蛋白突变的后果以及锥体镶嵌物的锥体和视觉系统功能的混乱。公共卫生相关性：我们的大多数视觉活动都依赖于视网膜中的锥形感受器。该建议采用多学科方法（使用高分辨率视网膜成像，遗传分析和电生理测试）来研究锥体色素中的突变如何影响锥形感受器的结构和功能。该提案中的工作将成为转化这种方法对其他视网膜变性研究的相同方法的基础，这将加速进步以有效实施新型疗法。