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: 8800023
• 负责人: Joseph Carroll
• 金额: $ 53.18万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-12-02 至 2018-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8800023
• 关键词: Abbreviations; Accounting; Address; Affect; Age related macular degeneration; Aging; Albinism; Anatomy; Animal Model; Area; Behavior; Behavioral; Blindness; Bruch' s basal membrane structure; Classification; Clinical; Color Visions; Computer Simulation; Cone; Data; Depth Perception; Development; Disease; Event; Eye; Fiber; Functional Magnetic Resonance Imaging; Genotype; Goals; Grant; Hair; Health; Human; Image; Imaging technology; Inborn Genetic Diseases; Individual; Iris; Knowledge; Lateral Geniculate Body; Length; Light; Link; Maps; Melanins; Membrane; Modeling; Modification; Molecular; Morphology; National Eye Institute; Nature; Neurobiology; Neurons; Nuclear; Ocular Albinism; Oculocutaneous Albinism; Ophthalmoscopy; Optic Chiasm; Optical Coherence Tomography; Outcome; Outcome Measure; Pathologic Nystagmus; Pathway interactions; Patients; Pattern; Peripheral; Phenotype; Photosensitivity; Pigments; Population; Psychophysics; Publications; Refractive Errors; Reporting; Research Personnel; Resolution; Retina; Retinal; Retinal Diseases; Retinal Ganglion Cells; Role; Scanning; Severities; Signal Transduction; Skin; Structure; Structure of retinal pigment epithelium; Technology; Testing; Textbooks; Thalamic structure; Therapeutic; Therapeutic Trials; Thick; Transillumination; Uncertainty; Variant; Vision; Vision research; Visual; Visual Acuity; Visual Cortex; Visual system structure; Work; adaptive optics; area striata; base; density; fovea centralis; improved; innovation; insight; interest; macula; multidisciplinary; non-invasive imaging; novel; novel therapeutics; pigment epithelium-derived factor; programs; public health relevance; receptive field; research study; retinotopic; sample fixation; tool; visual process; visual processing

DESCRIPTION (provided by applicant): Even though the fovea occupies only 0.02% of the total area of the retina, 40% of primary visual cortex is devoted to processing visual signals that arise there. Thus, it is not surprising that diseases affecting the structure or function of the foea are especially devastating to visually guided behaviors. Yet fundamental gaps remain in our concepts of how the fovea develops, how foveal structure is disrupted during aging and disease, and how the fovea interacts with more central visual system structures to determine key features of visual function. The overall goal of this proposal is to address these issues using a novel combination of noninvasive imaging technologies including functional magnetic resonance imaging (fMRI), optical coherence tomography (OCT) and adaptive optics scanning light ophthalmoscopy (AOSLO). Albinism is an inherited disorder characterized by absent or reduced melanin pigment in the eye, and often in the skin and hair, with all types manifesting the visual features of foveal hypoplasia, macular translucency, photosensitivity, refractive errors, nystagmus, impaired stereopsis, altered retinostriate decussation, and reduced visual acuity. These specific retinal and cortical features of albinism make it a perfect "experiment of nature" to examine the knowledge gaps listed above. We propose to do this through the following specific aims: 1) Define the spectrum of foveal morphology in albinism and assess the relationship between pit morphology and retinal melanin, 2) Identify retinal factors contributing t visual deficits in albinism, and 3) Determine the cortical correlates of visual deficits in albinis. The results of this project will provide a more comprehensive understanding of the interrelationships linking melanin, retinal morphology, and cortical organization. This will offer insight into the basis for vision deficits in albinism, which may alter current phenotype/genotype classifications. This work is expected to have a significant positive impact by providing a new framework for understanding and targeting clinical therapies to alleviate the behavioral manifestations of albinism, and by producing sensitive tools for assessing therapeutic outcomes. This proposal directly addresses emerging needs outlined in the National Eye Institute's August 2012 Publication, "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.

描述（由申请人提供）：尽管中央凹仅占视网膜总面积的0.02%，但40%的初级视觉皮层致力于处理视觉信号， 出现在那里。因此，这并不奇怪，影响foea的结构或功能的疾病对视觉引导的行为尤其具有破坏性。然而，在我们的概念中仍然存在根本性的差距，即中央凹如何发展，中央凹结构如何在衰老和疾病期间被破坏，以及中央凹如何与更中央的视觉系统结构相互作用以确定视觉功能的关键特征。本提案的总体目标是使用非侵入性成像技术（包括功能性磁共振成像（fMRI）、光学相干断层扫描（OCT）和自适应光学扫描光检眼镜（AOSLO））的新组合来解决这些问题。白化病是一种遗传性疾病，其特征在于眼睛中的黑色素缺失或减少，并且通常在皮肤和毛发中，所有类型都表现出中心凹发育不全、黄斑不透明、光敏性、屈光不正、眼球震颤、立体视觉受损、视网膜横纹交叉改变和视力降低的视觉特征。白化病的这些特定视网膜和皮质特征使其成为一个完美的“自然实验”，以检查上述知识差距。我们建议通过以下具体目标来做到这一点：1）定义白化病的中央凹形态谱，并评估小凹形态与视网膜黑色素之间的关系，2）确定白化病视觉缺陷的视网膜因素，以及3）确定白化病视觉缺陷的皮质相关性。这个项目的结果将提供一个更全面的了解黑色素，视网膜形态和皮质组织之间的相互关系。这将提供深入了解白化病的视力缺陷的基础，这可能会改变目前的表型/基因型分类。这项工作预计将有一个显着的积极影响，通过提供一个新的框架，了解和针对临床治疗，以减轻白化病的行为表现，并通过生产敏感的工具，评估治疗结果。该提案直接解决了国家眼科研究所2012年8月出版物“Vision Research：Needs，Gap，& Opportunities”中概述的新兴需求，并纳入了NEI视网膜疾病小组的具体计划目标：（1）表征视网膜的黄斑和中央凹周围区域，以更好地了解黄斑对疾病的偏好。(2)提高对神经元活动和分子事件在发育过程中中央视觉回路形成中的作用的理解。(3)继续开发和应用非侵入性技术，如fMRI，OCT，自适应光学和共聚焦成像，以更好地了解视网膜功能和疾病状态的变化。