Retinal Contributions to Vision Loss in Albinism

视网膜对白化病视力丧失的影响

基本信息

  • 批准号:
    10464283
  • 负责人:
  • 金额:
    $ 61.43万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-07-01 至 2026-06-30
  • 项目状态:
    未结题

项目摘要

The fovea is arguably the most important part of the human retina. The normal fovea is characterized by an excavation of inner retinal layers (leaving behind the foveal pit and a concomitant avascular zone), an increased density of cone photoreceptors with nearly absent rods, and specialized “private line” circuitry between cones and midget retinal ganglion cells. Together, these specializations provide the basis for our high-acuity photopic vision. Patients with albinism have disrupted foveal anatomy, with visual deficits including variably reduced acuity, increased photosensitivity, high refractive errors, nystagmus, and impaired stereopsis. Despite the prevalence of albinism (~1 in 15,000), significant gaps remain in our understanding of the anatomical basis for the visual deficits in albinism. Such gaps not only compromise our ability to develop novel therapeutic strategies for patients with albinism but also fundamentally limit our understanding of how the retina interacts with central visual structures to determine key features of normal visual function. We have formed a multidisciplinary research team whose overall goal is to close these knowledge gaps through execution of the following specific aims: 1) Examine the influence of retinal melanin on visual acuity and the phenotypic spectrum of foveal morphology, 2) Characterize disruptions in foveal post-receptoral circuitry in subjects with albinism, and 3) Map rod photoreceptor mosaic topography in subjects with albinism. By advancing non-invasive imaging approaches that can reveal the physiological basis for visual deficits in albinism on a personalized basis, we gain access to outcome measures for use in emerging therapeutic trials and develop the ability to define the therapeutic potential for individual patients. Clinically, such approaches are broadly applicable to diseases beyond albinism. This work is also expected to have a significant positive impact by increasing our basic understanding of the relationships between melanin, foveal anatomy, photoreceptor topography, retinal circuitry, and visual function. These relationships inform the basic developmental and organizational principles of the human visual system. Importantly, our proposal directly addresses emerging needs outlined in the most recent publication from the National Eye Institute, “Vision Research: Needs, Gaps, & Opportunities”, and incorporates specific program objectives of the NEI Retinal Diseases Panel: (1) Characterize the macula and perifoveal regions of the retina to better understand the predilection of the macula for disease; (2) Improve understanding of the roles of neuronal activity and molecular events in the formation of central visual circuits during development; (3) Continue to develop and apply noninvasive technologies such as fMRI, OCT, adaptive optics, and confocal imaging to better understand retinal function and changes in disease states. Altogether, this project takes a multidisciplinary approach towards elucidating how retinal structures contribute to vision deficits and reduced quality of life in patients suffering from albinism and related vision disorders.
中央凹可以说是人类视网膜最重要的部分。正常中央凹的特征在于 视网膜内层的凹陷(留下中心凹和伴随的无血管区), 视锥光感受器的密度,几乎没有视杆细胞,视锥细胞之间有专门的“专用线路”电路 和侏儒视网膜神经节细胞。总之,这些专业化为我们的高敏度明视提供了基础。 视野白化病患者的视网膜中央凹解剖结构被破坏, 视力、光敏性增加、高度屈光不正、眼球震颤和立体视觉受损。尽管 白化病的患病率(~1/15,000),我们对白化病的解剖学基础的理解仍然存在重大差距。 白化病患者的视觉缺陷这些差距不仅损害了我们开发新的治疗策略的能力, 但也从根本上限制了我们对视网膜如何与中枢神经系统相互作用的理解。 视觉结构,以确定正常视觉功能的关键特征。我们成立了一个多学科的 一个研究团队,其总体目标是通过执行以下内容来弥补这些知识差距 具体目的:1)检测视网膜黑色素对视力和中央凹表型谱的影响 形态学,2)表征白化病受试者的中央凹后感受器回路的中断,以及3)映射 白化病患者视杆细胞镶嵌地形图。通过推进非侵入性成像方法 这可以揭示白化病视觉缺陷的生理基础上个性化的基础上,我们获得访问 用于新兴治疗试验的结局指标,并开发定义治疗 个体患者的潜力。临床上,这种方法广泛适用于白化病以外的疾病。 预计这项工作也将产生重大的积极影响,增加我们对 黑色素、中央凹解剖学、光感受器地形图、视网膜回路和视觉功能之间的关系。 这些关系告知人类视觉的基本发展和组织原则 系统重要的是,我们的提案直接解决了最近出版物中概述的新需求 来自国家眼科研究所,“视力研究:需求,差距和机会”,并结合了具体的 NEI视网膜疾病小组的计划目标:(1)表征视网膜病变的黄斑和中央凹周围区域。 视网膜,以更好地了解黄斑疾病的偏好;(2)提高对视网膜疾病的作用的理解。 发育过程中中枢视觉回路形成中的神经元活动和分子事件;(3)继续 开发和应用非侵入性技术,如功能磁共振成像,OCT,自适应光学和共焦成像, 更好地了解视网膜功能和疾病状态的变化。总之,该项目需要一个多学科的 阐明视网膜结构如何导致视力缺陷和生活质量下降的方法 患有白化病和相关视力障碍的患者。

项目成果

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Joseph Carroll其他文献

Joseph Carroll的其他文献

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{{ truncateString('Joseph Carroll', 18)}}的其他基金

NAC Attack AOSLO Reading Center
NAC 攻击 AOSLO 阅读中心
  • 批准号:
    10593914
  • 财政年份:
    2022
  • 资助金额:
    $ 61.43万
  • 项目类别:
Retinal Contributions to Vision Loss in Albinism
视网膜对白化病视力丧失的影响
  • 批准号:
    10652487
  • 财政年份:
    2022
  • 资助金额:
    $ 61.43万
  • 项目类别:
NAC Attack AOSLO Reading Center
NAC 攻击 AOSLO 阅读中心
  • 批准号:
    10334337
  • 财政年份:
    2022
  • 资助金额:
    $ 61.43万
  • 项目类别:
Developing Cone-Dominant Retinal Disease Models as a Resource for Translational Vision Research
开发视锥细胞为主的视网膜疾病模型作为转化视觉研究的资源
  • 批准号:
    10477216
  • 财政年份:
    2018
  • 资助金额:
    $ 61.43万
  • 项目类别:
Developing Cone-Dominant Retinal Disease Models as a Resource for Translational Vision Research
开发视锥细胞为主的视网膜疾病模型作为转化视觉研究的资源
  • 批准号:
    10013200
  • 财政年份:
    2018
  • 资助金额:
    $ 61.43万
  • 项目类别:
Developing Cone-Dominant Retinal Disease Models as a Resource for Translational Vision Research
开发视锥细胞为主的视网膜疾病模型作为转化视觉研究的资源
  • 批准号:
    10631293
  • 财政年份:
    2018
  • 资助金额:
    $ 61.43万
  • 项目类别:
Developing Cone-Dominant Retinal Disease Models as a Resource for Translational Vision Research
开发视锥细胞为主的视网膜疾病模型作为转化视觉研究的资源
  • 批准号:
    10238804
  • 财政年份:
    2018
  • 资助金额:
    $ 61.43万
  • 项目类别:
Platform Technologies for Microscopic Retinal Imaging: Development & Translation
显微视网膜成像平台技术:开发
  • 批准号:
    9059095
  • 财政年份:
    2015
  • 资助金额:
    $ 61.43万
  • 项目类别:
Platform Technologies for Microscopic Retinal Imaging: Development & Translation
显微视网膜成像平台技术:开发
  • 批准号:
    8912125
  • 财政年份:
    2015
  • 资助金额:
    $ 61.43万
  • 项目类别:
Retinal Versus Cortical Contributions to Vision Loss in Albinism
视网膜与皮质对白化病视力丧失的影响
  • 批准号:
    9388351
  • 财政年份:
    2014
  • 资助金额:
    $ 61.43万
  • 项目类别:

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