Human Connectomes for Low Vision, Blindness, and Sight Restoration

 描述(申请人提供)：在全球范围内，超过2.85亿人视力受损，其中3900万人失明。视力障碍(失明和低视力)严重影响生活质量。针对一些致盲疾病的新视力恢复疗法已经问世。一种电子视网膜假体被批准用于晚期视网膜色素变性的视力恢复。基因治疗试验显示，莱伯氏先天性黑色素是有希望的。干细胞治疗老年性黄斑变性正在开始临床试验。在某些情况下，已经证明了显著的结果，这表明在长期失明后，至少部分视力恢复是可能的。然而，来自临床试验的心理物理数据往往显示出很大的结果差异。与中央视觉通路(CVP)相关的大脑结构和功能的前置条件可能是导致某些差异的原因。完全失明对大脑的影响已经得到了很好的研究，但大多数眼科疾病在视网膜上产生的影响因点对点而不同。眼病的精确地形图是如何映射到大脑的变化的？获得性视网膜损伤是否与CVP结构和功能的局部影响有关？这些视力丧失对中心静脉压的影响有可逆的吗？我们建议通过将先进的视网膜成像与人类连接组计划(HCP)中开发的大脑映射技术相结合，使用新颖而稳健的分析方法来回答这些问题，我们认为这些问题对于正在进行的视力恢复治疗的努力至关重要。我们将在致盲疾病及其治疗的自然过程中，以前所未有的细节揭示视网膜病理及其对中心静脉压的下游影响之间的关系。我们将向研究界提供一系列致盲疾病的视网膜病理原始和处理数据，以及通过HCP方案收集的神经成像数据。我们将提供用于从视网膜和神经数据集中提取相关特征的计算机代码以及将两者联系在一起的统计模型。广泛的数据集和相关的数据分析工具将为与视觉相关的神经可塑性研究奠定变革性的基础 损伤和视力恢复。

 DESCRIPTION (provided by applicant): Worldwide, over 285 million people are visually impaired, and 39 million of those are blind. Visual impairments (blindness and low vision) severely and negatively impact the quality of life. New sight-restoration treatments have arrived for some blinding diseases. An electronic retinal prosthesis is approved for sight restoration in advanced retinitis pigmentosa. Gene therapy trials have shown promise for Leber's congenital amaurosis. Stem cell treatments for age-related macular degeneration are starting clinical trials. In some cases, remarkable results have been demonstrated, suggesting that at least partial vision restoration is possible after prolonged blindness. However, psychophysical data from clinical trials often show large variance in outcomes. Preconditions in brain structure and function associated with the central visual pathway (CVP) may underlie some of the variance. The effect of complete blindness upon the brain is well studied, but most ophthalmologic disease produces effects that vary from point-to-point across the retina. How does the precise topography of eye disease map onto changes in brain? Is acquired retinal damage related to local effects upon the structure and function of the CVP? Are any of these effects of vision loss on the CVP reversible? We propose to answer these questions, which we believe are crucial to the on-going efforts in developing sight- restoration treatments, by combining advanced retinal imaging with the brain-mapping techniques developed in the Human Connectome Project (HCP), using novel yet robust analytical methods. We will reveal the relationships between retinal pathology and their downstream impact on the CVP in unprecedented detail over the natural courses of blinding diseases and their treatments. We will make available to the research community the raw and processed data on retinal pathology for a range of blinding diseases, along with neuroimaging data collected with the HCP protocol. We will provide the computer codes used to extract relevant features from the retinal and neural datasets and the statistical models that relate the two. The extensive datasets and the associated data-analysis tools will form a transformative foundation for studies of neural plasticity associated with visual impairments and sight restoration.