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），眼部相干断层扫描，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”。本建议的总体目的是表征正常和患病视网膜中的锥镶嵌的地形，以检查可能支配这种地形的因素，并评估这些镶嵌中的感光功能。我发现了与视锥细胞色素突变有关的新的视锥细胞变性机制。在这个建议中的实验将有助于澄清锥色素表达的破坏的有害影响，无论是对锥马赛克的外观和视觉性能。这项建议是努力建立一个研究计划的第一步，该计划将有助于理解锥视觉和视觉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，本提案中开发的方法学方法将可用于性质更复杂的其他视网膜疾病。通过一个独特的合作努力，我建议结合联合收割机的心理物理，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），以解决以下目标：具体目标1 -表征S-锥亚马赛克在正常和tritan科目及其关系的整体地形的视网膜。具体目标2 -检查L/M-染色质基因阵列中的突变对视锥细胞的活力和光感受器镶嵌体的组织的影响。具体目标3 -确定视锥细胞视蛋白突变和视锥细胞嵌合体解体对视锥细胞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中的视锥细胞。该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）来研究锥色素中的突变如何影响锥光感受器的结构和功能。该提案中的工作将作为将相同方法转化为未来其他视网膜变性研究的基础，这将加速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.