MEASURE OF RECEPTOR AND POST RECEPTOR ACTIVITY

受体和受体后活性的测量

• 批准号: 6518460
• 负责人: DONALD C. HOOD
• 金额: $ 28.53万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-05-01 至 2003-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6518460
• 关键词: amacrine cells; bioimaging /biomedical imaging; clinical research; cone cell; electroretinography; glaucoma; human subject; light adaptations; mathematical model; model design /development; noninvasive diagnosis; retina degeneration; retinal ganglion; rod cell; statistics /biometry; visual photoreceptor; visual phototransduction; visual stimulus

DESCRIPTION ( from the abstract ): The investigators' 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, they have shown that the usefulness of the ERG can be extended. Their initial observation that the leading edge of the rod a-wave could be described by the same models fitted to single receptor recordings has led to numerous studies of normal and abnormal retinal activity in humans and in animal models of retinal diseases. As part of aim 1 (INNER RETINA, MF-ERG), they propose to examine the contribution of the inner retina, which includes amacrine and ganglion cells, to a local measure of retinal activity, the cone multifocal ERG. Glaucoma, one of the leading causes of blindness, affects these cells. Current behavioral and electrophysiological procedures for detecting early signs of retinal damage are less than optimal. The investigators believe that they have found a very promising approach to this problem. The approach includes studies involving: a. monkeys in which inner retinal activity is pharmacologically blocked, b. normal human subjects, c. patients with glaucoma, and d. mathematical and statistical work. During the current grant period, they have developed procedures for measuring the response of the human rod receptor and for studying rod on-bipolars. Aim 2 (UTILIZE TECHNIQUES DEVELOPED IN CURRENT GRANT PERIOD) is to study the activity of the normal and abnormal human rod on-bipolar with these techniques. Further, they will develop a technique for measuring the waveform of the cone photoreceptor response (that is, deactivation) and will use it to study light adaptation and retinal diseases of the cone system. A third aim (DEVELOP TECHNIQUES FOR ASSESSING INL ACTIVITY IN NL AND ABN RETINAS) is to develop techniques for assessing inner nuclear layer (INL) activity of normal and abnormal retinas. While knowledge of the rod ERG is approaching the point where a computational model may be feasible, in comparison, less in known about the contributions of the bipolar cells to the human cone ERG. Here the investigators attack this problem with studies involving: a. monkeys in which INL activity is pharmacologically dissected, b. normal human subjects, c. patients with disease of the INL, and d. mathematical work.

描述（摘自摘要）：研究人员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，他们证明 ERG 的用途可以得到扩展。他们最初观察到杆状 a 波的前缘可以通过适合单个受体记录的相同模型来描述，这导致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（内视网膜，MF-ERG）的一部分，他们建议检查内视网膜（包括无长突细胞和神经节细胞）对视网膜活动局部测量（锥体多焦点 ERG）的贡献。青光眼是导致失明的主要原因之一，会影响这些细胞。目前用于检测视网膜损伤早期迹象的行为和电生理程序并不理想。研究人员相信他们已经找到了解决这个问题的非常有希望的方法。该方法包括涉及以下方面的研究： 猴子的内部视网膜活动被药物阻断，b．正常人类受试者，c.青光眼患者，d．数学和统计工作。在当前的资助期内，他们开发了测量人类视杆细胞受体反应和研究视杆细胞双极的程序。目标 2（利用当前资助期间开发的技术）是利用这些技术研究正常和异常人体杆在双极上的活动。此外，他们将开发一种测量视锥细胞感光反应（即失活）波形的技术，并将用它来研究视锥细胞系统的光适应和视网膜疾病。第三个目标（开发评估 NL 和 ABN 视网膜 INL 活动的技术）是开发评估正常和异常视网膜内核层 (INL) 活动的技术。虽然对视杆细胞 ERG 的了解已接近计算模型可行的程​​度，但相比之下，人们对双极细胞对人体视锥细胞 ERG 的贡献知之甚少。在这里，研究人员通过研究来解决这个问题，涉及：对 INL 活性进行药理学分析的猴子，b．正常人类受试者，c. 患有 INL 疾病的患者，以及 d．数学工作。