Measures of Human Receptor and Post Receptor Activity

人类受体和受体后活性的测量

基本信息

批准号：
7345359
负责人：
DONALD C. HOOD
金额：
$ 28.96万
依托单位：
COLUMBIA UNIV NEW YORK MORNINGSIDE
依托单位国家：
美国
项目类别：
财政年份：
1991
资助国家：
美国
起止时间：
1991-05-01 至 2009-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7345359
关键词：
Affect Animal Experimentation Animal Model Animals Behavioral Betula Genus Blindness Cells Clinical Clinical Trials Collaborations Cornea Data Diagnosis Disease Electrodes Electroretinography Fishes Ganglia Glaucoma Grant Human Inner Nuclear Layer Ischemia Laboratories Lead Localized Disease Measures Monkeys Mutation Myxoid cyst Noise Outcome Measure Patients Pattern Perimetry Pharmaceutical Preparations Phase Phototransduction Physiology Procedures Process Publications Purpose Reporting Research Personnel Retina Retinal Retinal Cone Retinal Diseases Scientist Signal Transduction Site Stimulus Sum Techniques Today Toxin Vertebrate Photoreceptors Visual Fields Work base cell injury cell type design ganglion cell human disease human study improved in vivo interest macula photoreceptor degeneration programs receptor response retinal damage retinal rods success transmission process

项目摘要

DESCRIPTION (provided by applicant): Our long-term objective has been to develop a set of noninvasive techniques for studying the physiology of the human retina. The electroretinogram (ERG), the summed activity of the retinal cells, is a noninvasive measure of retinal activity. The ERG has long been used for diagnosing and following the course of retinal diseases. By building upon discoveries made by the retinal physiologist, we have extended the usefulness of the ERG for mechanistic studies of human disease. In particular, we have developed procedures for studying both the activation and deactivation phases of phototransduction as well as for studying the activity of bipolar cells. This work has lead to numerous studies of normal and abnormal retinal activity in humans and in animal models of retinal diseases. As part of aim 1, we intend to explore possible ERG measures of ganglion cell activity. Glaucoma, one of the leading causes of blindness, affects these cells. Current behavioral and electrophysiological procedures for detecting early signs of ganglion ceil damage are less than optimal. There are considerable data from retinal physiology, and recent claims based on clinical evidence from other groups, to suggest that pattern stimuli and/or stimuli near cone ERG threshold (the photopic negative response) may provide the measure needed. We propose a way to assess these claims. As part of aim 2, we improve on the techniques we have already developed and apply them to: the study of cone deactivation in mutations known to affect the receptors, the study of inner nuclear layer activity in diseases affecting receptor transmission and/or bipolar cell responses and the study of localized diseases affecting primarily the macular region. Static perimetric visual fields and 30 Hz full-field flicker ERGs are leading candidates for primary outcome measure in trials involving diseases of the receptors (e.g. RP). We have a very poor understanding of how these measures are related either to each other or to local retinal damage. We propose as part of aim 3 to improve our understanding of these relationships as well as to improve our analysis of visual field data.

描述（由申请人提供）：我们的长期目标是开发一套用于研究人类视网膜生理学的非侵入性技术。视网膜电图（ERG）是视网膜细胞活动的总和，是视网膜活动的无创测量。 ERG 长期以来一直用于诊断和跟踪视网膜疾病的病程。通过以视网膜生理学家的发现为基础，我们扩展了 ERG 在人类疾病机制研究中的用途。特别是，我们开发了用于研究光转导的激活和失活阶段以及研究双极细胞活性的程序。这项工作引发了对人类和视网膜疾病动物模型中正常和异常视网膜活动的大量研究。作为目标 1 的一部分，我们打算探索神经节细胞活性的可能 ERG 测量。青光眼是导致失明的主要原因之一，会影响这些细胞。目前用于检测神经节细胞损伤早期迹象的行为和电生理程序并不理想。来自视网膜生理学的大量数据以及最近基于其他群体的临床证据的主张表明，模式刺激和/或接近锥体 ERG 阈值（明视阴性反应）的刺激可能提供所需的测量。我们提出了一种评估这些主张的方法。作为目标 2 的一部分，我们改进了已经开发的技术并将其应用于：已知影响受体的突变中锥体失活的研究、影响受体传递和/或双极细胞的疾病中内核层活性的研究主要影响黄斑区域的局部疾病的反应和研究。静态视野视野和 30 Hz 全视野闪烁 ERG 是涉及受体疾病（例如 RP）的试验中主要结果测量的主要候选者。我们对这些措施之间的相互关系或与局部视网膜损伤之间的关系知之甚少。作为目标 3 的一部分，我们建议提高我们对这些关系的理解，并提高我们对视野数据的分析。