OCT Measurement of Trabecular Meshwork Function In Vivo

体内小梁网功能的 OCT 测量

基本信息

  • 批准号:
    10480756
  • 负责人:
  • 金额:
    $ 62.14万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-08-01 至 2024-07-31
  • 项目状态:
    已结题

项目摘要

Project Summary/Abstract Glaucoma is a major cause of blindness and current treatments are insufficient. A major and the only treatable risk factor for glaucoma is elevated intraocular pressure (IOP), which is usually due to trabecular meshwork (TM) dysfunction. Remarkably, techniques for directly assessing the most relevant measure of TM function, i.e. outflow facility, have not changed for 60+ years, are patient-unfriendly, and are rarely used clinically. Our prior work has established a correlation between TM stiffness and outflow facility in human and mouse eyes, strongly implicating TM stiffness as a surrogate measure of TM function. Here it is proposed to develop and validate a novel OCT-based method to measure TM stiffness in patients as an indirect indicator of TM function, an approach we term “21st century tonography”. The key idea is to image the TM and Schlemm’s canal as IOP is manipulated. Based on these images, unbiased (automated) OCT image segmentation will be used to quantify the change of Schlemm’s canal luminal size as a function of IOP, and then engineering analysis techniques (inverse finite element modeling) will be employed to quantify the stiffness of the TM in the living eye. The proposal’s preliminary data strongly suggest that this approach is feasible. Thus, the overall objective is to validate the approach, which will be achieved through two specific aims. The first uses mouse models and the second uses human eyes. In Aim 1, we will build on our extensive experience in imaging the mouse outflow tract with OCT in normotensive animals and in two clinically-relevant established models of ocular hypertension. The resulting TM stiffness measurements will be validated against direct measurements of TM stiffness using our established protocol based on atomic force microscopy, and against longitudinal IOP and outflow facility measurements. In Aim 2, we will carry out analogous studies in human eyes, first using perfused human anterior segments where the tissue can be extensively manipulated, and then moving to clinical studies in patients with ocular hypertension/early glaucoma. An important aspect of all proposed studies is that the effects of a clinically- available rho-kinase inhibitor (netarsudil) on TM stiffness, TM function, and IOP will be longitudinally assessed, strengthening clinical relevant and impact. It is expected, as suggested by the strong preliminary data, that the proposed OCT-based approach to measuring TM stiffness and TM function will be shown to be valid. This project is highly innovative, since it will create a novel, non-invasive tool to interrogate TM function in human subjects, the first such tool since the introduction of tonography six decades ago. Such a tool will be useful in multiple contexts, including: (1) basic science studies of TM function and physiology; and (2) longitudinal evaluation of novel emerging treatments to repair TM function, including small molecule-based therapies, gene therapy approaches for restoring TM function, and stem cell-based therapies for the TM.
项目摘要/摘要 青光眼是导致失明的主要原因,目前的治疗方法不足。一个严重的,也是唯一可以治疗的 青光眼的危险因素是眼压升高,这通常是由于小梁网(TM)引起的。 功能障碍。值得注意的是,直接评估TM功能的最相关度量,即流出的技术 设施,60多年没有改变,对病人不友好,很少在临床上使用。我们之前的工作是 在人和小鼠的眼睛中建立了TM硬度和流出能力之间的相关性,这强烈地暗示了 TM硬度作为TM函数的替代度量。 在这里,建议开发和验证一种新的基于OCT的方法来测量AS患者的TM硬度 TM功能的间接指标,我们称之为“21世纪色调”。关键的想法是形象地 作为眼压的TM和Schlemm管被操纵。基于这些图像,无偏(自动)OCT图像 分割将被用来量化Schlemm管管腔大小随眼压的变化,然后 工程分析技术(逆有限元建模)将被用来量化 活着的眼睛里的TM。 该提案的初步数据有力地表明,这种方法是可行的。因此,总体目标是 验证该方法,这将通过两个具体目标来实现。第一种使用鼠标模型和 第二种是用人眼。在目标1中,我们将建立我们在对小鼠流出道成像方面的丰富经验 在血压正常的动物和两个临床相关的高眼压模型中使用OCT。这个 由此产生的TM硬度测量将与TM硬度的直接测量进行验证,使用我们的 建立了基于原子力显微镜的方案,并针对纵向眼压和流出设施 测量。在目标2中,我们将在人眼中进行类似的研究,首先使用灌流的人类前房 组织可以被广泛操纵的节段,然后转移到临床研究中 高眼压/早期青光眼。所有拟议研究的一个重要方面是,临床上- 可用的Rho-Kinase抑制剂(Netarsudil)对TM僵硬、TM功能和眼压进行纵向评估, 加强临床相关性和影响力。正如强劲的初步数据所表明的,预计 提出的基于OCT的TM刚度和TM函数的测量方法将被证明是有效的。 该项目具有很高的创新性,因为它将创造一种新的、非侵入性的工具来询问人类的TM功能 主题,这是自60年前引入色调印刷以来的第一个这样的工具。这样的工具将在以下方面有用 多重背景,包括:(1)TM功能和生理的基础科学研究;(2)纵向 评估新出现的修复TM功能的治疗方法,包括基于小分子的治疗方法、基因 恢复TM功能的治疗方法,以及TM的干细胞疗法。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

C ROSS ETHIER其他文献

C ROSS ETHIER的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('C ROSS ETHIER', 18)}}的其他基金

Mechanisms of axial elongation in myopia
近视眼轴伸长的机制
  • 批准号:
    10344059
  • 财政年份:
    2022
  • 资助金额:
    $ 62.14万
  • 项目类别:
Mechanisms of axial elongation in myopia
近视眼轴伸长的机制
  • 批准号:
    10844969
  • 财政年份:
    2022
  • 资助金额:
    $ 62.14万
  • 项目类别:
Transcriptional and Biomechanical Analysis of Segmental Outflow in Glaucoma
青光眼节段流出的转录和生物力学分析
  • 批准号:
    10327834
  • 财政年份:
    2021
  • 资助金额:
    $ 62.14万
  • 项目类别:
Schlemm’s canal on a chip: A platform for screening a novel class of glaucoma medications
施莱姆氏管芯片:用于筛选新型青光眼药物的平台
  • 批准号:
    10475283
  • 财政年份:
    2021
  • 资助金额:
    $ 62.14万
  • 项目类别:
Schlemm’s canal on a chip: A platform for screening a novel class of glaucoma medications
施莱姆氏管芯片:用于筛选新型青光眼药物的平台
  • 批准号:
    10293948
  • 财政年份:
    2021
  • 资助金额:
    $ 62.14万
  • 项目类别:
OCT Measurement of Trabecular Meshwork Function In Vivo
体内小梁网功能的 OCT 测量
  • 批准号:
    10706947
  • 财政年份:
    2020
  • 资助金额:
    $ 62.14万
  • 项目类别:
OCT Measurement of Trabecular Meshwork Function In Vivo
体内小梁网功能的 OCT 测量
  • 批准号:
    10222709
  • 财政年份:
    2020
  • 资助金额:
    $ 62.14万
  • 项目类别:
OCT Measurement of Trabecular Meshwork Function In Vivo
体内小梁网功能的 OCT 测量
  • 批准号:
    10032714
  • 财政年份:
    2020
  • 资助金额:
    $ 62.14万
  • 项目类别:
Targeting Scleral Stiffness as a Novel Therapeutic Approach in Glaucoma
针对巩膜僵硬作为青光眼治疗的新方法
  • 批准号:
    9044787
  • 财政年份:
    2015
  • 资助金额:
    $ 62.14万
  • 项目类别:
Targeting Scleral Stiffness as a Novel Therapeutic Approach in Glaucoma
针对巩膜僵硬作为青光眼治疗的新方法
  • 批准号:
    9248387
  • 财政年份:
    2015
  • 资助金额:
    $ 62.14万
  • 项目类别:

相似海外基金

Life outside institutions: histories of mental health aftercare 1900 - 1960
机构外的生活:1900 - 1960 年心理健康善后护理的历史
  • 批准号:
    DP240100640
  • 财政年份:
    2024
  • 资助金额:
    $ 62.14万
  • 项目类别:
    Discovery Projects
Development of a program to promote psychological independence support in the aftercare of children's homes
制定一项计划,促进儿童之家善后护理中的心理独立支持
  • 批准号:
    23K01889
  • 财政年份:
    2023
  • 资助金额:
    $ 62.14万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Integrating Smoking Cessation in Tattoo Aftercare
将戒烟融入纹身后护理中
  • 批准号:
    10452217
  • 财政年份:
    2022
  • 资助金额:
    $ 62.14万
  • 项目类别:
Integrating Smoking Cessation in Tattoo Aftercare
将戒烟融入纹身后护理中
  • 批准号:
    10670838
  • 财政年份:
    2022
  • 资助金额:
    $ 62.14万
  • 项目类别:
Aftercare for young people: A sociological study of resource opportunities
年轻人的善后护理:资源机会的社会学研究
  • 批准号:
    DP200100492
  • 财政年份:
    2020
  • 资助金额:
    $ 62.14万
  • 项目类别:
    Discovery Projects
Creating a National Aftercare Strategy for Survivors of Pediatric Cancer
为小儿癌症幸存者制定国家善后护理策略
  • 批准号:
    407264
  • 财政年份:
    2019
  • 资助金额:
    $ 62.14万
  • 项目类别:
    Operating Grants
Aftercare of green infrastructure: creating algorithm for resolving human-bird conflicts
绿色基础设施的善后工作:创建解决人鸟冲突的算法
  • 批准号:
    18K18240
  • 财政年份:
    2018
  • 资助金额:
    $ 62.14万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
Development of an aftercare model for children who have experienced invasive procedures
为经历过侵入性手术的儿童开发善后护理模型
  • 批准号:
    17K12379
  • 财政年份:
    2017
  • 资助金额:
    $ 62.14万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Development of a Comprehensive Aftercare Program for children's self-reliance support facility
为儿童自力更生支持设施制定综合善后护理计划
  • 批准号:
    17K13937
  • 财政年份:
    2017
  • 资助金额:
    $ 62.14万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
Project#2 Extending Treatment Effects Through an Adaptive Aftercare Intervention
项目
  • 批准号:
    8742767
  • 财政年份:
    2014
  • 资助金额:
    $ 62.14万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了