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

Marrocco, E.; Esposito, F.; Tarallo, V.; Carboncino, A.; Alvino, F. G.; De Falco, S.; Franco, B.; De Risi, M.; Indrieri, A.; Surace, E. M.; De Leonibus, E.

doi:10.1101/760603

bioRxiv · 10.1101/760603

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

Marrocco, E.·Esposito, F.·Tarallo, V.·Carboncino, A.·Alvino, F. G.·De Falco, S.·Franco, B.·De Risi, M.·Indrieri, A.·Surace, E. M.·De Leonibus, E.

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Abstract

Introduction-synuclein aggregates have been identified in the retina of Parkinsons disease patients associated to vision impairment. In this study, we sought to determine the effects of -synuclein overexpression on the survival and function of dopaminergic (DA) amacrine cells in the retina.\n\nMethodsAdult mice were intravitreally injected with an adeno-associated viral (AAV) vector to overexpress human wild-type -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.\n\nResults-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.\n\nConclusionsThe data show that -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.

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Marrocco, E., Esposito, F., Tarallo, V., Carboncino, A., Alvino, F. G., De Falco, S., Franco, B., De Risi, M., Indrieri, A., Surace, E. M., De Leonibus, E.. 2019-09-08. α-synuclein in the retina leads to degeneration of dopamine amacrine cells impairing vision. https://doi.org/10.1101/760603

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