α-synuclein overexpression in the retina leads to vision impairment and degeneration of dopaminergic amacrine cells

Sci Rep. 2020 Jun 15;10(1):9619. doi: 10.1038/s41598-020-66497-6.

Abstract

The presence of α-synuclein aggregates in the retina of Parkinson's disease patients has been associated with vision impairment. In this study we sought to determine the effects of α-synuclein overexpression on the survival and function of dopaminergic amacrine cells (DACs) in the retina. Adult mice were intravitreally injected with an adeno-associated viral (AAV) vector to overexpress human wild-type α-synuclein in the inner retina. Before and after systemic injections of levodopa (L-DOPA), retinal responses and visual acuity-driven behavior were measured by electroretinography (ERG) and a water maze task, respectively. Amacrine cells and ganglion cells were counted at different time points after the injection. α-synuclein overexpression led to an early loss of DACs associated with a decrease of light-adapted ERG responses and visual acuity that could be rescued by systemic injections of L-DOPA. The data show that α-synuclein overexpression affects dopamine neurons in the retina. The approach provides a novel accessible method to model the underlying mechanisms implicated in the pathogenesis of synucleinopathies and for testing novel treatments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amacrine Cells / metabolism*
  • Amacrine Cells / pathology
  • Animals
  • Dopaminergic Neurons / metabolism*
  • Dopaminergic Neurons / pathology
  • Female
  • Fluorescent Antibody Technique
  • Levodopa / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Retina / drug effects
  • Retina / metabolism*
  • Retina / pathology
  • Retinal Degeneration / metabolism*
  • Retinal Degeneration / pathology
  • Vision Disorders / metabolism*
  • Vision Disorders / pathology
  • Visual Acuity
  • alpha-Synuclein / metabolism*

Substances

  • alpha-Synuclein
  • Levodopa