Using vision as a window into Parkinson's Disease

虽然帕金森氏症通常被认为是一种运动障碍，但它的特征也是视力变化。使用源于人类视觉科学的方法，我们已经证明了已知的导致早发性帕金森氏症的突变会导致果蝇(果蝇)视觉系统的过度兴奋。反过来，随着果蝇年龄的增长，这会导致兴奋毒性和视力丧失。将这一方法解释回人类，我们的初步发现表明，在帕金森氏症患者中观察到了同样的视觉系统变化。因此，我们认为视力可以提供一个可靠的生物标志物，可以用来诊断和监测帕金森病的进展。这个跨学科的翻译项目将把用于药物发现筛选和解剖疾病基础的分子机制的动物(果蝇)模型与人类参与者的研究结合起来，以优化和翻译这一方案，用作临床诊断工具。你将常驻谢菲尔德翻译神经科学研究所(SITraN)，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个屋檐下。与果蝇神经退行性变模型专家Ryan West(SITraN)博士合作，您将在果蝇模型中识别出缓解帕金森氏症表型(包括视觉功能障碍)的新化合物。你还将利用果蝇的先进遗传工具箱来剖析支撑疾病的分子机制。与约克神经成像中心(YNiC)的Alex Wade(York)教授合作，您将把在果蝇身上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，特别关注视觉处理的早期阶段：亮度、颜色和对比度的提取。一旦建立了这些测试，您将在大脑和行为实验室与Melanie Burke博士(利兹)合作，在人类参与者身上开发这些测试的临床适用版本，使用脑成像(FNIRS)和眼动测量来确定他们对帕金森氏症的敏感性。

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.