NIAR01AG004058 Research Supplements to Promote Diversity in Health-Related Research

NIAR01AG004058 促进健康相关研究多样性的研究补充剂

基本信息

批准号：
8855231
负责人：
JOHN S WERNER
金额：
$ 3.68万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-01 至 2016-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8855231
关键词：
Affect Age Age related macular degeneration Aging Alleles Area Basic Science Behavioral Clinical Color Complement Factor H Cone Custom Data Diabetic Retinopathy Dimensions Disease Drusen Elderly Electroretinography Evaluation Eye Financial compensation Foundations Functional disorder Genes Health Human Image Individual Life Light Coagulation Longevity Measures Methods Modeling Morphology Nature Neuronal Plasticity Opsin Optics Pathway interactions Patients Perception Performance Photoreceptors Play Process Property Psychophysics Recovery Relative (related person)Research Retina Retinal Retinal Diseases Retinal Ganglion Cells Role Shapes Short Waves Signal Transduction Site Staging Stimulus Testing Time Vertebrate Photoreceptors Vision Visual Visual Pathways Visual system structure adaptive optics age related design experience ganglion cell neuromechanism normal aging novel programs public health relevance relating to nervous system research study response retinal adaptation senescence spatial vision ultra high resolution visual coding visual optics visual performance visual process visual processing

项目摘要

DESCRIPTION (provided by applicant): Senescent changes in human vision have been well documented, but the factors responsible for these changes are only partially understood. The proposed research is intended to provide fundamental data on aging of the human visual system using methods that separate the relative contributions of optical and neural mechanisms. This research builds on a program demonstrating that age-related losses in the visual pathways have a profound effect on early stage processing but are compensated to a surprising degree to maintain constancy of perception. The overarching theme of the proposed research is to understand temporal dynamics of adaptation, compensation and neuroplasticity at several time scales and levels of processing. Aim 1 compares normal aging and early-stage age-related macular degeneration. Temporal dynamics and retinal adaptation mechanisms will be studied under scotopic and photopic conditions using the full-field and multifocal ERG. Response interactions will be analyzed to understand functional sites of aging and adaptation in the outer retina. These functional data will be correlated with sequenced opsin genes and complement factor H alleles, and with ultra-high resolution images to study photoreceptor numbers and outer retinal morphology, including relations with drusen. Aim 2 will explore temporal dynamics and gain mechanisms under conditions that are dominated by the response of magno-, parvo- or konio-cellular pathways. The hypothesis to be tested is that the OFF subdivisions of these pathways are affected more in senescence than are the ON subdivisions. This will be evaluated by measuring a psychophysical impulse response function and by a psychophysical probe to quantify age-related changes in gain control mechanisms of magno- and parvo-cellular pathways. Aim 3 is concerned with putative cortical compensation mechanisms. While most methods define the adaptation midpoint, the first experiment for this aim is concerned with how adaptation adjusts the range or variance of color signals along cardinal and higher-order color axes. A second study will measure adaptation to higher- order ocular aberrations using a custom adaptive optics phoropter. Finally, patients with diabetic retinopathy will be tested following retinal photocoagulation therapy to determine whether some losses in vision are compensated by expansion of areas subserving spatial summation, similarly to enlargements of spatial summation areas associated with age-related losses in photoreceptors and ganglion cells. These experiments are guided by current hypotheses about the manner in which visual performance may be affected by normal senescence and by age-related macular degeneration and diabetic retinopathy. In addition to providing basic data on the aging visual system, the experiments will provide probes for models of how the visual system adapts and compensates for degradations in the optical and neural images that occur with senescence and disease.

描述（由申请人提供）：人类视力中的衰老变化已得到充分记录，但是仅部分理解了这些变化的因素。拟议的研究旨在使用分离光学和神经机制的相对贡献的方法提供有关人类视觉系统衰老的基本数据。这项研究基于一个计划，表明视觉途径中与年龄相关的损失对早期处理具有深远的影响，但在保持感知恒定的程度上得到了令人惊讶的程度。拟议的研究的总体主题是在几个时间尺度和处理水平上了解适应，补偿和神经塑性的时间动态。 AIM 1比较正常的衰老和早期年龄相关的黄斑变性。时间动力学和视网膜适应机制将在Scotopic和Photopic条件下使用全场和多焦点ERG进行研究。将分析响应相互作用，以了解外视网膜中衰老和适应的功能部位。这些功能数据将与测序的Opsin基因和补体HERELES以及超高分辨率图像相关，以研究光感受器数量和视网膜外形态，包括与Drusen的关系。 AIM 2将探索时间动力学和增益机制，这些条件以磁性，parvo-或Konio-Collular途径的响应为主。要检验的假设是，这些途径的关闭细分在衰老中的影响比ON细分更大。这将通过测量心理物理脉冲反应函数和心理物理探针来评估这一点，以量化与年龄相关的巨型和粒细胞途径的增益控制机制的变化。 AIM 3与假定的皮质补偿机制有关。尽管大多数方法定义了适应中点，但此目标的第一个实验涉及适应如何调节沿红外和高阶颜色轴的颜色信号的范围或方差。第二项研究将使用自定义的自适应光学纤维来测量对高阶眼畸变的适应。最后，在视网膜光凝治疗后将测试患有糖尿病性视网膜病变的患者，以确定视力损失是否通过扩展空间总和的区域的扩展来补偿，这类似于与光感受器和神经节细胞中与年龄相关的空间相关损失相关的空间求和区域的扩大。这些实验是由目前关于视觉性能可能受正常衰老以及与年龄相关的黄斑变性和糖尿病性视网膜病影响的方式的假设的指导。除了提供有关老化视觉系统的基本数据外，实验还将为视觉系统如何适应和补偿衰老和疾病发生的光学和神经图像中的降解。