Retinal α-synuclein deposits in Parkinson’s disease patients and animal models

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.LV and LDG are supported by the Research Foundation Flanders (fellowships 1S51718N and 12I3817N). IOL acknowledges financial support from the Ministerio de Educación, Spain (FPU 14/03166). NC acknowledges financial support from the Ministerio de Economía y Competitividad, Spain (MINECO-FEDER-BFU2015-67139-R), Generalitat Valenciana (Prometeo 2016/158), and Instituto Carlos III (ISCIII RETICS-FEDER RD16/0008/0016). The Brain and Body Donation Program has been supported by the National Institute of Neurological Disorders and Stroke (U24 NS072026), the National Institute on Aging (P30 AG19610), the Arizona Department of Health Services, the Arizona Biomedical Research Commission, and the Michael J. Fox Foundation for Parkinson’s Research