Retinal Versus Cortical Contributions to Vision Loss in Albinism

描述(申请人提供)：尽管中心凹只占视网膜总面积的0.02%，但40%的初级视觉皮质用于处理视觉信号， 站在那里。因此，影响前庭结构或功能的疾病对视觉引导行为尤其具有破坏性也就不足为奇了。然而，我们对中心凹如何发育，中心凹结构如何在衰老和疾病中被破坏，以及中心凹如何与更中央的视觉系统结构相互作用来确定视觉功能的关键特征的概念仍然存在根本的差距。这项提案的总体目标是使用包括功能磁共振成像(FMRI)、光学相干断层扫描(OCT)和自适应光学扫描光眼底检查(AOSLO)在内的非侵入性成像技术的新组合来解决这些问题。白化病是一种遗传性疾病，其特征是眼部黑色素缺失或减少，常见于皮肤和头发，所有类型的白化病都表现为中心凹发育不良、黄斑半透明、光敏、屈光不正、眼球震颤、立体视功能受损、视网膜条纹交叉改变和视力下降。白化病的这些特定的视网膜和皮质特征使其成为检验上面列出的知识差距的完美“自然实验”。我们建议通过以下具体目标来完成这项工作：1)定义白化病中心凹形态的光谱，并评估凹陷形态与视网膜黑色素之间的关系；2)识别导致白化病视觉缺陷的视网膜因素；3)确定白化病视觉缺陷的皮质相关因素。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。这将提供对白化病视力缺陷的基础的洞察，这可能改变当前的表型/基因分类。这项工作预计将产生重大的积极影响，为理解和针对临床治疗提供一个新的框架，以减轻白化病的行为表现，并产生评估治疗结果的敏感工具。这项建议直接满足了美国国家眼科研究所2012年8月出版的《视力研究：需求、差距和机遇》中概述的新兴需求，并纳入了NEI视网膜疾病小组的具体项目目标：(1)描述视网膜黄斑和视网膜中央凹周围区域的特征，以更好地了解黄斑易患疾病的原因。(2)提高对神经元活动和分子事件在发育过程中中枢视觉回路形成中的作用的理解。(3)继续开发和应用fMRI、OCT、自适应光学、共焦成像等非侵入性技术，以更好地了解视网膜功能和疾病状态的变化。

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.