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

Introduction: alpha-synuclein aggregates have been identified in the retina of Parkinson9s disease patients associated to vision impairment. In this study, we sought to determine the effects of alpha-synuclein overexpression on the survival and function of dopaminergic (DA) amacrine cells in the retina. Methods: Adult mice were intravitreally injected with an adeno-associated viral (AAV) vector to overexpress human wild-type alpha-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. Results: alpha-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. Conclusions: The data show that alpha-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.