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.

中央凹可以说是人类视网膜最重要的部分。正常的中央凹的特点是 视网膜内层的挖掘（留下中央凹坑和伴随的无血管区），增加 视杆细胞几乎不存在的视锥细胞的密度，以及视锥细胞之间专门的“专用线”电路 和侏儒视网膜神经节细胞。这些专业化共同为我们的高敏锐度明视奠定了基础 想象。白化病患者的中心凹解剖结构受到破坏，视力缺陷包括不同程度的视力下降 视力下降、光敏性增加、屈光不正高、眼球震颤和立体视觉受损。尽管 尽管白化病的患病率很高（约 15,000 人中就有 1 人），但我们对白化病的解剖学基础的理解仍存在重大差距 白化病的视力缺陷。这种差距不仅损害了我们开发新治疗策略的能力 对于白化病患者来说，但也从根本上限制了我们对视网膜如何与中枢相互作用的理解 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 研究团队的总体目标是通过执行以下措施来缩小这些知识差距 具体目标： 1) 检查视网膜黑色素对视力和黄斑中心凹表型谱的影响 形态学，2) 表征白化病受试者黄斑中心凹后感受器回路的破坏，以及 3) 地图 白化病受试者的视杆光感受器马赛克地形。通过推进非侵入性成像方法 可以个性化地揭示白化病视觉缺陷的生理基础，我们可以获得 用于新兴治疗试验的结果测量，并培养定义治疗方法的能力 个别患者的潜力。在临床上，此类方法广泛适用于白化病以外的疾病。 这项工作预计还将通过增加我们对 黑色素、中心凹解剖结构、光感受器地形、视网膜电路和视觉功能之间的关系。 这些关系揭示了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新出版物中概述的新需求 来自国家眼科研究所的“视觉研究：需求、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) 描述黄斑和黄斑中心凹周围区域的特征 视网膜，以更好地了解黄斑部疾病的倾向； (2) 加深对角色的理解 发育过程中中央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 fMRI、OCT、自适应光学和共焦成像等非侵入性技术 更好地了解视网膜功能和疾病状态的变化。总而言之，这个项目需要多学科的支持 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。