Expression of α‐Synuclein in the mouse retina is confined to inhibitory presynaptic elements

Abstract

Abstractα‐Synuclein (α‐Syn) is enriched in presynaptic terminals of the central nervous system including the retina and plays a role in the synaptic vesicle cycle and synaptic transmission. Abnormal aggregation of α‐Syn is considered to be the main component of the Lewy bodies that are the pathological hallmarks of Parkinson's disease. Although expression pattern of α‐Syn has been described in the retinas, its precise cellular and subcellular locations are poorly understood. We investigated the precise expression of α‐Syn using light microscopy (LM) and electron microscopy (EM) with antibodies against α‐Syn in the mouse retina. We found that the majority of α‐Syn immunoreactivity (IR) is located in GABAergic, glycinergic, and dopaminergic amacrine cells, and their processes often make a direct synapse to other labeled or unlabeled amacrine profiles, bipolar cell terminals, or ganglion cell dendrites. Further, our LM and immuno‐EM results confirm the absence of α‐Syn in excitatory photoreceptors, bipolar cell bodies, and their ribbon synapses, providing evidence, for the first time, that ribbon synapses do not express α‐Syn. Additionally, α‐Syn IR is located in the ganglion cells, some of which are intrinsically photosensitive retinal ganglion cells. These results reveal a previously unappreciated inhibitory synapse‐specific expression pattern of α‐Syn in the retina, suggesting that α‐Syn may play a distinct role in the modulation and integration of inhibitory synaptic transmission in the retina.