MEASURES OF HUMAN RECEPTOR AND POST RECEPTOR ACTIVITY

人类受体和受体后活性的测量

• 批准号: 7726320
• 负责人: DONALD C. HOOD
• 金额: $ 38.8万
• 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 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7726320
• 关键词: Affect; Anatomy; Axon; Betula Genus; Blindness; Cells; Clinical; Clinical Research; Clinical Trials; Collaborations; Computer software; Cornea; Data; Data Set; Degenerative Disorder; Development; Disease; Effectiveness; Electrodes; Electroretinography; Eye; Fishes; Frequencies; Ganglion Cell Layer; Genetic; Grant; Health; Human; Laboratories; Lasers; Life; Measurement; Measures; Mediating; Modeling; Monitor; Ophthalmologist; Optical Coherence Tomography; Patients; Pattern; Performance; Perimetry; Photoreceptors; Phototransduction; Positioning Attribute; Procedures; Prosthesis; Receptor Cell; Relative (related person); Research; Research Personnel; Retina; Retinal; Retinal Cone; Retinal Degeneration; Retinal Diseases; Retinal Ganglion Cells; Retinitis Pigmentosa; Scanning; Structure; Techniques; Testing; Therapeutic; Thick; Time; Treatment Efficacy; Vertebrate Photoreceptors; Vision; Visual Fields; Work; alternative treatment; behavior measurement; functional loss; in vivo; indexing; loss of function; meetings; novel; polarimetry; public health relevance; receptor; receptor function; retinal nerve fiber layer; retinal rods; success; theories

DESCRIPTION (provided by applicant): Our long-term objective has been to develop a set of noninvasive techniques for studying the human retina. By applying novel techniques and current theories of phototransduction to the full-field electroretinogram (ERG), we have successfully developed widely-used noninvasive techniques for studying the global activity of the rod and cone receptors, as well as the rod bipolar cells. However, many of the planned and/or anticipated clinical trials involving diseases of the receptors require localized measures of retinal function for evaluating treatment efficacy. In the past, we have worked with the two most popular techniques for measuring local retinal activity, the multifocal electroretinogram (mfERG) and, static automated perimetry (SAP), the behavioral measure of local sensitivity of the visual field. Because these techniques have severe limitations for use in clinical trials, we have turned to a new noninvasive technique for measuring the structure (anatomy) of the retina, frequency domain optical coherence tomography (fdOCT). As part of Aim 1, we intend to explore the relationship between a fdOCT measure of the loss of receptors and the loss of visual function, as measured with SAP and mfERGs, in corresponding regions of the field. These data will allow for the testing of hypotheses about the functional consequences of different genetic types of retinitis pigmentosa (RP) and other types of retinal degenerative diseases. A quantitative comparison of the fdOCT measures to visual field loss will allow us to evaluate the utility of the fdOCT for use in clinical trials. Therapeutic and prosthetic approaches to the treatment of diseases of the receptors depend upon viable post-receptor cells, especially retinal ganglion cells (RGCs) and their axons. Current techniques are not able to make this assessment in patients with diseases of the receptors, as they depend upon functioning receptors. As part of Aim 2, we will assess the structural integrity of post receptor cells, especially (RGCs) and their axons using fdOCT. In addition, to better understand these measurements, patients will be studied with a different noninvasive technique for measuring retinal anatomy, scanning laser polarimetry. Finally, as part of Aim 3, we develop a unique approach and generate a unique data set for evaluating the performance of commercial fdOCT machines and computer software, which purport to measure specific retinal layers. PUBLIC HEALTH RELEVANCE: Many retinal diseases cause blindness by attacking the photoreceptors while others attack post-receptor cells. We are developing noninvasive techniques for assessing the mechanisms by which a disease affects different retinal cells. These same techniques can enable the ophthalmologist to monitor the health of these cells and, thus the effectiveness of alternative treatments.

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的无创技术。通过将新型技术和当前的光转移理论应用于全场电图（ERG），我们成功地开发了广泛使用的非侵入性技术，用于研究杆和锥体受体的全球活性以及杆双极细胞。但是，许多涉及受体疾病的计划和/或预期的临床试验都需要视网膜功能的局部测量，以评估治疗疗效。过去，我们曾使用两种最受欢迎​​的技术，用于测量局部视网膜活动，多焦点电视图（MFERG）和静态自动化局部（SAP），即视野局部灵敏度的行为度量。由于这些技术在临床试验中具有严重的局限性，因此我们转向了一种测量视网膜频域光学相干断层扫描（FDOCT）结构（解剖）的新无创技术。作为AIM 1的一部分，我们打算探索在相应区域中使用SAP和MFERG测量的受体丧失和视觉功能丧失的FDOCT度量之间的关系。这些数据将允许对不同遗传类型的色素性视网膜炎（RP）和其他类型的视网膜退行性疾病的功能后果进行测试。 FDOCT度量与视野损失的定量比较将使我们能够评估FDOCT在临床试验中使用的实用性。治疗受体疾病的治疗方法和假肢方法取决于感受器后细胞，尤其是视网膜神经节细胞（RGC）及其轴突。当前的技术无法在受体疾病的患者中进行评估，因为它们取决于受体的功能。作为AIM 2的一部分，我们将使用FDOCT评估受体细胞的结构完整性，尤其是（RGC）及其轴突。此外，为了更好地了解这些测量值，将使用一种不同的非侵入性技术来测量视网膜解剖结构，扫描激光偏振仪。最后，作为AIM 3的一部分，我们开发了一种独特的方法，并生成了一个独特的数据集，以评估商用FDOCT机器和计算机软件的性能，该计算机和计算机软件旨在测量特定的视网膜层。公共卫生相关性：许多视网膜疾病通过攻击感光器而攻击受体后细胞，从而引起失明。我们正在开发无创技术来评估疾病影响不同的视网膜细胞的机制。这些相同的技术可以使眼科医生能够监测这些细胞的健康状况，从而可以替代治疗的有效性。