MEASURES OF HUMAN RECEPTOR AND POST RECEPTOR ACTIVITY

人类受体和受体后活性的测量

• 批准号: 8293613
• 负责人: DAVID G BIRCH
• 金额: $ 57.98万
• 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 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8293613
• 关键词: Affect; Age related macular degeneration; Anatomy; Area; Atrophic; Basic Science; Betula Genus; Blindness; Cells; Clinic; Clinical; Clinical Trials; Collaborations; Computational algorithm; Computer software; Country; Development; Disease; Disease Progression; Effectiveness; Electroretinography; Eye; Fishes; Frequencies; Fundus; Fundus photography; Future; Goals; Grant; Health; Human; Image; Laboratories; Life; Macular degeneration; Measurement; Measures; Mediating; Methods; Modeling; Monitor; Ophthalmologist; Optical Coherence Tomography; Outcome Measure; Patients; Perimetry; Photoreceptors; Phototransduction; Positioning Attribute; Receptor Cell; Research; Research Personnel; Retina; Retinal; Retinal Cone; Retinal Diseases; Retinitis Pigmentosa; Scanning; Stargardt' s disease; Structure; Techniques; Testing; Time; Treatment Efficacy; Vertebrate Photoreceptors; Vision; Visual Acuity; Visual Fields; Work; alternative treatment; cost; disorder of macula of retina; effective therapy; efficacy testing; extrastriate visual cortex; geographic atrophy; improved; in vivo; indexing; interest; macula; novel; primary outcome; receptor; retinal rods; standard measure; success; theories; treatment trial

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. These indices of objective retinal function can be appropriate outcome measures for treatment trials with systemically-administered agents. However, many ongoing and anticipated clinical trials involving diseases of the receptors require localized measures of retinal function, such as the multifocal ERG and static automated perimetry, for evaluating treatment efficacy. These tests, however, are difficult to administer, time consuming, and not patient friendly, plus, as typically used, assess only cone function. Due to recent developments in retinal imaging, we can now relate these functional measures directly to underlying structure. We have been focusing our efforts on a new noninvasive technique for measuring the structure (anatomy) of the retina, frequency domain optical coherence tomography (fdOCT). This work, supported by the current grant, has benefitted from our novel quantitative approaches to assessing segmentation of retinal layers seen on fdOCT scans. As part of Aim 1, we evaluate and improve our fdOCT measures of disease related damage to the photoreceptors and test the efficacy of these measures in the clinic. This includes developing and evaluating new methods for quantifying fdOCT scans. We use these methods to test hypotheses about disease mechanisms, as well as models of disease progression. In addition, we propose to test the hypothesis that a particular fdOCT measure (i.e. the IS/OS contour) can provide a better measure of disease progression than current standard measures for diseases such as retinitis pigmentosa (RP). As part of Aim 2, we extend our approach to diseases of the macula, the region of greatest importance to normal visual function. Motivated by evidence that diseases of the macula may affect the rods first, we seek to determine the relationship between fundus perimetric measures of rod function and fdOCT measures of receptor integrity in patients with early age-related macular degeneration (AMD), geographic atrophy, and Stargardt disease. We will test the hypothesis that rod fundus perimetry and fdOCT are more sensitive to progression in these diseases than visual acuity or measures of the area of atrophy on fundus photography. The inherent variability in current functional measures of progression in RP and diseases of the macula is a substantial deterrent to efforts to develop effective treatments. Costs become prohibitive due to the large numbers of patients and extensive trial durations that are required. Determining the utility and validity of fdOCT in RP, and its relationship to measures of local rod- and cone-mediated function in macular disease, could profoundly enhance the feasibility of future clinical trials in these diseases. 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。这些客观视网膜功能的指标可能是针对全身管理剂的治疗试验的适当结果指标。但是，许多涉及受体疾病的持续和预期的临床试验需要视网膜功能的局部测量，例如多焦点ERG和静态自动化周围，以评估治疗功效。但是，这些测试难以管理，耗时，并且不友好，另外，通常使用的是仅评估锥功能。由于视网膜成像的最新发展，我们现在可以将这些功能度量直接与基础结构联系起来。我们一直将精力集中在一种新的无创技术上，用于测量视网膜，频域光学相干断层扫描（FDOCT）的结构（解剖）。这项工作得到了当前赠款的支持，从我们新颖的定量方法中受益，以评估FDOCT扫描中看到的视网膜层的细分。 作为AIM 1的一部分，我们评估并改善了对疾病对感光体损害的FDOCT度量，并测试临床中这些措施的功效。这包括开发和评估用于量化FDOCT扫描的新方法。我们使用这些方法来检验有关疾病机制以及疾病进展模型的假设。此外，我们建议检验以下假设：与当前疾病（例如色素性视网膜炎（RP））相比，特定的FDOCT测量（即IS/OS轮廓）可以更好地衡量疾病进展的措施。 作为AIM 2的一部分，我们将方法扩展到黄斑的疾病，这是对正常视觉功能最重要的区域。通过证据表明黄斑疾病可能首先影响棒的证据，我们试图确定杆功能的眼底量表与早期年龄相关的黄斑变性（AMD），地理萎缩和Stargardt疾病的患者中的棒功能测量和FDOCT测量之间的关系。我们将检验以下假设：与视力敏锐度或眼底摄影的萎缩面积相比，杆状的外部和FDOCT对这些疾病进展更敏感。 RP和黄斑疾病的当前功能量度的固有差异是对开发有效治疗的努力的实质性威慑。由于大量患者和需要大量的试验持续时间，成本变得越来越高。确定FDOCT在RP中的效用和有效性，及其与黄斑疾病中局部杆和锥体介导的功能的关系的关系可以深刻地提高这些疾病中未来临床试验的可行性。 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。