Transgenic mouse models overexpressing α-syn show an accumulation of the protein in specific retinal cells depending on the promoter used for the expression 9. Α-syn aggregates have been identified in the retina of PD patients and in particular in the Ganglion Cell Layer (GCL), the Inner Plexiform Layer (IPL) and the Inner Nuclear Layer (INL) 8. The clinical observations that PD patients also have visual symptoms such as reduced visual acuity, low contrast sensitivity, altered electroretinogram (ERG) and disturbed color vision 4, 5, 6, 7 have led to the retina being considered as a potential biomarker for PD. Indeed, recombinant adeno-associated viral vector (rAAV)-mediated overexpression of human wild-type (WT) α-syn in the midbrain of adult rodents leads to progressive loss of nigral dopaminergic neurons 2, 3. Experimental evidence in animal models established a causal link between α-syn overexpression or mutations and the degeneration of dopaminergic neurons. The two hallmarks of Parkinson’s disease (PD) are the formation of α-synuclein (α-syn ) inclusions into Lewy bodies (LBs) 1 and the degeneration of the nigrostriatal dopaminergic system leading to motor and cognitive deficits. The approach provides a novel accessible method to model the underlying mechanisms implicated in the pathogenesis of synucleinopathies and for testing novel treatments. The data show that α-synuclein overexpression affects dopamine neurons in the retina. 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. Amacrine cells and ganglion cells were counted at different time points after the injection. 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. Adult mice were intravitreally injected with an adeno-associated viral (AAV) vector to overexpress human wild-type α-synuclein in the inner retina. 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. The presence of α-synuclein aggregates in the retina of Parkinson’s disease patients has been associated with vision impairment.
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