NIAR01AG004058 Research Supplements to Promote Diversity in Health-Related Research

描述（由申请人提供）：人类视力的衰老变化已被充分记录，但导致这些变化的因素仅被部分理解。该研究旨在通过分离光学和神经机制的相对贡献的方法，为人类视觉系统的衰老提供基础数据。这项研究建立在一个项目的基础上，该项目表明，与年龄相关的视觉通路的丧失对早期处理有深远的影响，但在维持感知的稳定性方面得到了惊人的补偿。本研究的主要目的是在不同的时间尺度和加工水平上理解适应、补偿和神经可塑性的时间动态。目的1比较正常衰老和早期年龄相关性黄斑变性。使用全视野和多焦点ERG研究暗光和光条件下的时间动力学和视网膜适应机制。将分析反应相互作用，以了解老化和适应外视网膜的功能位点。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，以研究光感受器数量和外视网膜形态，包括与醉酒的关系。目的2将探讨时间动力学和增益机制的条件下，主要是由马尼奥，细小或konio-细胞途径的反应。要测试的假设是，这些途径的OFF细分比ON细分在衰老中受到的影响更大。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，以量化与年龄相关的磁细胞和细小细胞通路增益控制机制的变化。目的3是关于假定的皮质补偿机制。虽然大多数方法都定义了自适应中点，但为此目的的第一个实验关注的是自适应如何沿基数和高阶颜色轴调整颜色信号的范围或方差。第二项研究将使用定制的自适应光学光镜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，以确定一些视力损失是否通过空间求和区域的扩张来补偿，类似于光感受器和神经节细胞中与年龄相关的空间求和区域的扩大。这些实验是根据目前关于视觉表现可能受到正常衰老、年龄相关性黄斑变性和糖尿病视网膜病变影响的假设进行的。除了提供老化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随着衰老和疾病而出现的光学和神经图像的退化的模型提供探测。

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.