α-synuclein in the retina leads to degeneration of dopamine amacrine cells impairing vision

Author:

Elena Marrocco,Federica Esposito,Valeria Tarallo,Anna Carboncino,Grazia Alvino Filomena,Sandro De Falco,Brunella Franco,Maria De Risi,Indrieri Alessia,Maria Surace Enrico,Elvira De Leonibus

Abstract

AbstractIntroductionα-synuclein aggregates have been identified in the retina of Parkinson’s disease patients associated to vision impairment. In this study, we sought to determine the effects of α-synuclein overexpression on the survival and function of dopaminergic (DA) amacrine cells in the retina.MethodsAdult mice were intravitreally injected with an adeno-associated viral (AAV) vector to overexpress human wild-type α-synuclein in the inner retina. Following systemic injections of levodopa (L-DOPA), retinal responses and visual acuity driven behavior were measured by electroretinography (ERG) and water maze task, respectively. Amacrine cells and ganglion cells were counted at 1, 2 and 3 months post-injection.Resultsα-synuclein led to an early loss of DA cells, which was associated with the decrease of light-adapted ERG responses and visual acuity. Systemic injections of L-DOPA rescued these retinal and visual abnormalities.ConclusionsThe data show that α-synuclein affects dopamine neurons in the retina. The approach provides a novel accessible mode of modeling the underlying mechanisms implicated in synucleinophaties pathogenesis and for testing novel treatments.

Publisher

Cold Spring Harbor Laboratory

Cited by 2 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Visual Impairments in Parkinson’s Disease;Neuroscience and Behavioral Physiology;2023-07

2. Visual disturbances in Parkinson’s disease;Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova;2022

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