Retinal Contributions to Vision Loss in Albinism

视网膜对白化病视力丧失的影响

• 批准号: 10464283
• 负责人: Joseph Carroll
• 金额: $ 61.43万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 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
• 来源: https://reporter.nih.gov/project-details/10464283
• 关键词: Abbreviations; Address; Albinism; Alleles; Anatomy; Angiography; Behavior; Behavioral; Blindness; Clinical; Color; Complex; Cone; Correlative Study; Data; Depth Perception; Development; Discrimination; Disease; Event; Eye; Fiber; Foundations; Functional Magnetic Resonance Imaging; Future; Ganglion Cell Layer; Genetic; Genotype; Goals; Hair; Health; Hereditary Disease; Human; Impairment; Individual; Interdisciplinary Study; Iris; Knowledge; Light; Link; Literature; Maps; Measurement; Melanins; Modeling; Molecular; Monophenol Monooxygenase; Morphology; Mosaicism; National Eye Institute; Neurons; Nuclear; Ocular Albinism; Oculocutaneous Albinism; Ophthalmoscopy; Optical Coherence Tomography; Outcome; Outcome Measure; Pathologic Nystagmus; Pathology; Patients; Phenotype; Photoreceptors; Photosensitivity; Physiological; Pigments; Prevalence; Privatization; Production; Publications; Quality of life; Recording of previous events; Refractive Errors; Reporting; Research Personnel; Resolution; Retina; Retinal Cone; Retinal Diseases; Retinal Ganglion Cells; Rod; Role; Scanning; Severities; Skin; Structure; Structure of retinal pigment epithelium; Technology; Testing; Therapeutic; Therapeutic Trials; Transillumination; Vision; Vision Disorders; Vision research; Visual; Visual Acuity; Visual system structure; Work; adaptive optics; adaptive optics scanning laser ophthalmoscopy; confocal imaging; density; fovea centralis; human subject; imaging approach; improved; individual patient; insight; interdisciplinary approach; interest; macula; multidisciplinary; non-invasive imaging; novel therapeutic intervention; optical imaging; patient population; programs; retinal imaging; retinal rods; tool

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.

可以说，中心凹是人类视网膜最重要的部分。正常的中心凹的特征是 视网膜内层的切开(留下中心凹和伴随的无血管区)，增加了 视锥感光器的密度几乎没有视杆，视锥之间有专门的“专线”电路 和侏儒视网膜神经节细胞。总而言之，这些专业知识为我们的高敏感度验光提供了基础 幻象。白化病患者的中心凹解剖受到破坏，视力障碍包括不同程度的减少。 视力、光敏性增强、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(15,000人中有1人)，在我们对白化病的解剖学基础的理解上仍然存在重大差距 白化病的视觉缺陷。这种差距不仅损害了我们开发新的治疗策略的能力 对于白化病患者，但也从根本上限制了我们对视网膜如何与中央 视觉结构决定正常视觉功能的关键特征。我们已经形成了一个多学科的 研究团队，其总体目标是通过执行以下任务来弥合这些知识差距 具体目标：1)检测视网膜黑色素对视力和中心凹表型谱的影响 形态学，2)白化病受试者中心凹接受后环路的特征，以及3)MAP 白化病患者的杆状感光感受器镶嵌地形图。通过发展非侵入性成像方法 可以在个性化的基础上揭示白化病视觉缺陷的生理基础，我们可以访问 在新出现的治疗试验中使用的结果衡量标准，并发展确定治疗方法的能力 对个别患者来说是有潜力的。临床上，这种方法广泛适用于白化病以外的疾病。 这项工作也有望产生重大的积极影响，通过增加我们对 黑色素、中心凹解剖、光感受器地形图、视网膜回路和视觉功能之间的关系。 这些关系构成了人类视觉的基本发展和组织原则 系统。重要的是，我们的建议直接满足了最新出版物中概述的新兴需求 来自国家眼科研究所的《视觉研究：需要、差距和机遇》，并纳入了具体的 NEI视网膜疾病小组的计划目标：(1)描述黄斑和视网膜中央凹周围区域的特征 视网膜以更好地了解黄斑的发病倾向；(2)提高对黄斑的作用的理解 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，以 更好地了解视网膜功能和疾病状态的变化。总的来说，这个项目需要一个多学科的 阐明视网膜结构如何导致视力障碍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。