Assessing Photoreceptor Structure and Function in Normal and Diseased Retina

描述(由申请人提供)：这项建议涉及NEI视网膜疾病小组的两个计划目标：“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，如功能磁共振成像(FMRI)、眼部相干断层扫描、自适应光学和共焦成像，以更好地了解视网膜功能和疾病状态的变化。这项建议的总体目的是描述正常和病变视网膜的视锥镶嵌的地形图，检查可能控制这种地形图的因素，并评估这些马赛克的光感受器功能。我发现了与锥体感光色素突变有关的新的锥体退化机制。这项提议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。这项建议是努力建立一个研究计划的第一步，该计划将有助于了解锥体视力和视力障碍的基本生物学过程。通过研究视锥马赛克中的地形破坏如何影响视觉功能(对比敏感度、敏锐度、敏感度)，我将在细胞水平上获得对结构-功能关系的新见解。此外，这项提案中开发的方法学方法将适用于性质更复杂的其他视网膜疾病。通过一项独特的合作努力，我建议将心理物理、电生理和遗传学技术与活体成像技术(如光学相干断层扫描和自适应光学眼底镜)相结合，以解决以下目标：特定目标1-表征正常和三角受试者的S视锥亚镶嵌及其与视网膜整体地形图的关系。特定目的2-检测L/M-光色素基因阵列突变对视锥细胞活性和光感受器马赛克组织的影响。具体目标3：确定视锥细胞突变和视锥细胞马赛克结构紊乱对视锥细胞和视觉系统功能的影响。与公共健康相关：我们的大部分视觉活动依赖于视网膜中的视锥感光细胞。这项建议采用多学科方法(使用高分辨率视网膜成像、基因分析和电生理测试)来研究视锥细胞色素突变如何影响视锥细胞感光细胞的结构和功能。这项建议中的工作将作为将这一相同方法转化为未来对其他视网膜变性的研究的基础，这将加快有效实施新疗法的进展。

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.