NIAR01AG004058 Research Supplements to Promote Diversity in Health-Related Research

描述（由申请人提供）：人类视觉的衰老变化已经有了很好的记录，但导致这些变化的因素只有部分了解。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老化的基础数据。这项研究建立在一个程序的基础上，该程序表明，视觉通路中与年龄相关的损失对早期处理有着深远的影响，但在令人惊讶的程度上得到了补偿，以保持感知的恒定性。拟议的研究的首要主题是了解适应，补偿和神经可塑性在几个时间尺度和处理水平的时间动态。目的1比较正常老化和早期年龄相关性黄斑变性。时间动力学和视网膜适应机制将在暗视和明视条件下使用全视野和多焦ERG进行研究。反应的相互作用将进行分析，以了解老化和适应的功能部位在外层视网膜。这些功能数据将与测序的视蛋白基因和补体因子H等位基因相关，并与超高分辨率图像相关，以研究感光细胞数量和外部视网膜形态，包括与玻璃疣的关系。目标2将探索时间动态和增益机制的条件下，主要是由大，小或konio细胞途径的反应。待检验的假设是，这些通路的OFF细分在衰老中比ON细分受到更多的影响。这将通过测量心理物理脉冲响应函数和心理物理探针来评估，以量化大细胞和小细胞通路的增益控制机制中与年龄相关的变化。目的3是关于假定的皮层补偿机制。虽然大多数方法定义的适应中点，第一个实验的目的是关注如何适应调整的范围或变化的颜色信号沿着基数和高阶颜色轴。第二项研究将使用定制的自适应光学综合屈光检查仪测量对高阶眼像差的适应。最后，糖尿病视网膜病变患者将在视网膜光凝治疗后进行测试，以确定视力的一些损失是否通过扩展空间总和的区域来补偿，类似于与光感受器和神经节细胞中年龄相关损失相关的空间总和区域的扩大。这些实验是由目前的假设，其中视觉性能可能会受到影响的方式正常衰老和年龄相关性黄斑变性和糖尿病视网膜病变。除了提供有关衰老视觉系统的基本数据外，这些实验还将为视觉系统如何适应和补偿衰老和疾病引起的光学和神经图像退化的模型提供探针。

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.