Research Group of Neural Circuit Development and Regeneration, Department of Biology, KU Leuven, Naamsestraat 61, Box 2464, Louvain, Belgium.
Department of Physiology, Genetics and Microbiology, University of Alicante, Alicante, Spain.
Acta Neuropathol. 2019 Mar;137(3):379-395. doi: 10.1007/s00401-018-01956-z. Epub 2019 Feb 5.
Despite decades of research, accurate diagnosis of Parkinson's disease remains a challenge, and disease-modifying treatments are still lacking. Research into the early (presymptomatic) stages of Parkinson's disease and the discovery of novel biomarkers is of utmost importance to reduce this burden and to come to a more accurate diagnosis at the very onset of the disease. Many have speculated that non-motor symptoms could provide a breakthrough in the quest for early biomarkers of Parkinson's disease, including the visual disturbances and retinal abnormalities that are seen in the majority of Parkinson's disease patients. An expanding number of clinical studies have investigated the use of in vivo assessments of retinal structure, electrophysiological function, and vision-driven tasks as novel means for identifying patients at risk that need further neurological examination and for longitudinal follow-up of disease progression in Parkinson's disease patients. Often, the results of these studies have been interpreted in relation to α-synuclein deposits and dopamine deficiency in the retina, mirroring the defining pathological features of Parkinson's disease in the brain. To better understand the visual defects seen in Parkinson's disease patients and to propel the use of retinal changes as biomarkers for Parkinson's disease, however, more conclusive neuropathological evidence for the presence of retinal α-synuclein aggregates, and its relation to the cerebral α-synuclein burden, is urgently needed. This review provides a comprehensive and critical overview of the research conducted to unveil α-synuclein aggregates in the retina of Parkinson's disease patients and animal models, and thereby aims to aid the ongoing discussion about the potential use of the retinal changes and/or visual symptoms as biomarkers for Parkinson's disease.
尽管已经进行了数十年的研究，但帕金森病的准确诊断仍然是一个挑战，而且仍然缺乏能够改变疾病进程的治疗方法。对帕金森病早期（无症状前）阶段的研究以及新生物标志物的发现对于减轻这种负担以及在疾病开始时更准确地诊断疾病至关重要。许多人推测，非运动症状可能为帕金森病的早期生物标志物研究提供突破，包括大多数帕金森病患者中出现的视觉障碍和视网膜异常。越来越多的临床研究调查了使用活体评估视网膜结构、电生理功能和视觉驱动任务作为识别有风险的患者的新方法，这些患者需要进一步进行神经检查，并对帕金森病患者的疾病进展进行纵向随访。通常，这些研究的结果与视网膜中的α-突触核蛋白沉积和多巴胺缺乏有关，反映了大脑中帕金森病的定义性病理特征。然而，为了更好地理解帕金森病患者的视觉缺陷，并推动将视网膜变化用作帕金森病的生物标志物，迫切需要更具结论性的神经病理学证据来证明视网膜中存在α-突触核蛋白聚集及其与大脑中α-突触核蛋白负担的关系。这篇综述全面而批判性地概述了为揭示帕金森病患者和动物模型视网膜中的α-突触核蛋白聚集而进行的研究，从而旨在帮助正在进行的关于将视网膜变化和/或视觉症状用作帕金森病生物标志物的潜在用途的讨论。
