Ribbon Synapses and Retinal Disease: Review

Abstract

Synaptic ribbons are presynaptic protein complexes that are believed to be important for the transmission of sensory information in the visual system. Ribbons are selectively associated with those synapses where graded changes in membrane potential drive continuous neurotransmitter release. Defective synaptic transmission can arise as a result of the mutagenesis of a single ribbon component. Visual diseases that stem from malfunctions in the presynaptic molecular machinery of ribbon synapses in the retina are rare. In this review, we provide an overview of synaptopathies that give rise to retinal malfunction and our present understanding of the mechanisms that underlie their pathogenesis and discuss muscular dystrophies that exhibit ribbon synapse involvement in the pathology.

Keywords: inherited retinal degeneration; presynaptic ribbon proteins; retina; retinal disorders; ribbon synapses.

Figure 1

Inherited retinal degeneration (IRD) is a common form of vision disease in humans. Characterized by photoreceptor degeneration, mutations in the represented elements of the ribbon synapse induce both nonsyndromic and syndromic forms of these diseases. The clinical manifestations of the diseases caused by these dysfunctions are diverse.

Figure 2

HRG4/Unc119 is expressed in the outer plexiform layer of murine retinas. Immunolabeling of ribbon synapses with (A) Ribeye (green) and (B) HRG4/Unc119 (red). (C) merged. Outer plexiform layer (A’–C’). Scale bar = 20 µm in (A–C) and 2 µm in (A’–C’).

Figure 3

Tulp1 is expressed through retinal photoreceptors where it interacts with Ribeye in the outer plexiform layer. Wildtype mouse retinas labeled with antibodies against (A) Ribeye (green) and (B) Tulp1 (red). Outer plexiform layer shown in (A’–C’). Scale bar = 20 µm in (A–C) and 2 µm in (A’–C’).

Figure 4

Calcium channels are localized to the outer plexiform layer where they are closely associated with ribbons at the synapse. Shown is antibody staining of an adult wildtype mouse retina labeled with (A) Ribeye (green) and (B) Calcium channel pore forming subunit, α1F (red). (C) merged. Outer plexiform layer shown in (A’–C’). Scale bar = 20 µm in (A–C) and 2 µm in (A’–C’).

Figure 5

Rim2 is expressed at the ribbon synapses of the OPL and the IPL in the mouse retina. Shown is antibody staining of an adult wildtype mouse retina labeled with (A) Ribeye (green) and (B) Rim2 (red). (C) merged. Outer plexiform layer shown in (A’–C’). Scale bar = 20 µm in (A–C) and 2 µm in (A’–C’).

Figure 6

Dystrophin expression in the mouse retina is localized to the outer plexiform layer of the retina where it complexes with dystroglycan. Shown is antibody staining of an adult wildtype mouse retina labeled with (A) Ribeye (green) and (B) dystrophin (red). (C). Merged. Outer plexiform layer shown in (A’–C’). Scale bar = 20 µm in (A–C) and 5µm in (A’–C’).

Figure 7

Dystroglycan is localized to the outer plexiform layer of the retina. Shown is antibody staining of an adult wildtype mouse retina labeled with (A) Ribeye (green) and (B) dystroglycan (red). (C) merged. Outer plexiform layer shown in (A’–C’). Retinal vasculature (arrows). Scale bar = 20 µm in (A–C) and 2 µm in (A’–C’).