Using vision as a window into Parkinson's Disease

虽然通常被认为是一种运动障碍，但帕金森氏症也以视力变化为特征。使用源自人类视觉科学的方法，我们已经表明，已知导致早发性帕金森病的突变导致果蝇（果蝇）视觉系统的过度兴奋性。随着果蝇年龄的增长，这反过来又会导致兴奋性毒性和视力丧失。将这种方法应用到人类身上，我们的初步发现表明，帕金森患者的视觉系统也发生了同样的变化。因此，我们建议视力可能提供一种可靠的生物标志物，可用于诊断和监测帕金森病的进展。这个跨学科的转化项目将结合动物（果蝇）模型进行药物发现筛选，并通过对人类参与者的研究来剖析疾病的分子机制，以优化和翻译该方案，作为临床诊断工具。你将在谢菲尔德转化神经科学研究所（SITraN）工作，这是一个充满活力的跨学科研究机构，将基础研究人员和临床医生聚集在一起。与果蝇神经变性模型专家Ryan West博士（SITraN）合作，您将在果蝇模型中识别缓解帕金森病表型（包括视觉功能障碍）的新化合物。您还将利用果蝇先进的遗传工具箱来剖析支持疾病的分子机制。与约克神经成像中心（YNiC）的Alex Wade教授（约克）合作，您将把果蝇中使用的分析转化为强大的神经成像测量（fMRI/MEG/EEG/fNIRS），可用于客观评估人类视觉系统的健康状况，特别关注“早期”视觉处理阶段：亮度，颜色和对比度的提取。一旦建立了这些检测方法，您将与大脑和行为实验室的Melanie Burke博士（利兹）合作，在人类参与者中开发临床适用的这些检测方法，使用脑成像（fNIRS）和眼动测量来确定他们对帕金森病的敏感性。

Whilst commonly considered to be a motor disorder, Parkinson's Disease is also characterised by changes in vision. Using methods derived from human vision science, we have shown that mutations known to cause early onset Parkinson's disease result in hyperexcitability in the Drosophila (fruit fly) visual system. This, in turn, leads to excitotoxicity and vision loss as the flies age. Translating this methodology back to humans, our preliminary findings show that the same changes in the visual system are observed in Parkinson's patients. We therefore propose that vision may provide a reliable biomarker that can be used to diagnose and monitor progression of Parkinson's disease. This interdisciplinary, translational project will combine animal (Drosophila) models for drug discovery screens and dissecting the molecular mechanisms underpinning disease with the study of human participants to optimise and translate this protocol for use as a clinical diagnostic tool. You will be based in the Sheffield Institute for translational neuroscience (SITraN) a vibrant interdisciplinary research institute bringing together both basic researchers and clinicians under one roof. Working with Dr Ryan West (SITraN), an expert in Drosophila models of neurodegeneration, you will identify novel compounds that alleviate Parkinson's disease phenotypes, including visual dysfunction, in Drosophila models. You will also utilise the advanced genetic toolbox of Drosophila to dissect the molecular mechanisms underpinning disease. Working with Professor Alex Wade (York) at the York Neuroimaging Centre (YNiC), you will translate the assays used in Drosophila into robust neuroimaging measurements (fMRI/MEG/EEG/fNIRS) that can be used to objectively assess the health of the human visual system with a particular focus on 'early' visual processing stages: the extraction of luminance, colour and contrast. Once these assays are established, you will work with Dr Melanie Burke (Leeds) in the Brain and Behaviour Lab to develop clinically appropriate versions of these assays in human participants, using brain imaging (fNIRS) and eye movement measures to establish their sensitivity to Parkinson's disease.