Assessing Photoreceptor Structure and Function in Normal and Diseased Retina

描述（由申请人提供）：该提案涉及NEI视网膜疾病小组的2个项目目标：“探索视网膜的地形和区域差异以及这种地形与疾病进展的关系”。-“继续开发和应用非侵入性技术，如功能性磁共振成像（fMRI）、眼相干断层扫描、自适应光学和共聚焦成像，以更好地了解视网膜功能和疾病状态的变化”。本提案的总体目的是表征正常和病变视网膜锥体马赛克的地形，检查可能控制这种地形的因素，并评估这些马赛克中的光感受器功能。我发现了新的锥体退化机制与锥体光色素突变有关。本提案中的实验将有助于阐明锥体色素表达中断对锥体马赛克外观和视觉表现的有害影响。这项提议是建立一个研究项目的第一步，该项目将有助于理解锥体视觉和视觉障碍背后的基本生物学过程。通过检查锥体马赛克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-功能关系获得新的见解。此外，在本建议中开发的方法方法将可翻译为其他性质更复杂的视网膜疾病。通过独特的合作努力，我建议将心理物理、电生理和遗传技术与体内成像技术（如光学相干断层扫描和自适应光学检眼镜）结合起来，以实现以下目标：具体目标1 -表征正常和异型受试者的s锥亚马赛克及其与视网膜整体地形的关系。具体目标2 -研究L/ m光色素基因阵列突变对视锥细胞活力和光感受器镶嵌组织的影响。具体目标3 -确定锥体视蛋白突变和锥体马赛克紊乱对锥体和视觉系统功能的影响。公共卫生相关性：我们的大部分视觉活动依赖于视网膜上的视锥感光器。本提案采用多学科方法（使用高分辨率视网膜成像，遗传分析和电生理测试）来研究视锥色素突变如何影响视锥光感受器结构和功能。本提案中的工作将作为将相同方法转化为其他视网膜变性的未来研究的基础，这将加速新疗法的有效实施。

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.