Restoration of synaptic function in sight for degenerative retinal disease
Timm Schubert, Bernd Wissinger
Timm Schubert, Bernd Wissinger
Published June 22, 2015
Citation Information: J Clin Invest. 2015;125(7):2572-2575. https://doi.org/10.1172/JCI82577.
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Commentary

Restoration of synaptic function in sight for degenerative retinal disease

Abstract

Synaptic disorganization is a prominent feature of many neurological diseases of the CNS, including Parkinson’s disease, intellectual development disorders, and autism. Although synaptic plasticity is critical for learning and memory, it is unclear whether this innate property helps restore synaptic function in disease once the primary cause of disease is abrogated. An answer to this question may come from a recent investigation in X-linked retinoschisis, a currently untreatable retinopathy. In this issue of the JCI, Ou, Vijayasarathy, and colleagues showed progressive disorganization of key functional elements of the synapse between photoreceptors and ON-bipolar cells in a retinoschisin-deficient mouse model. Moreover, they demonstrated that adeno-associated virus–mediated (AAV-mediated) delivery of the retinoschisin gene restores structure and function to the photoreceptor to ON–bipolar cell synapse in mouse models, even in adults at advanced stages of the disease. The results of this study hold promise that AAV-based supplemental gene therapy will benefit patients with X-linked retinoschisis in a forthcoming clinical trial.

Authors

Timm Schubert, Bernd Wissinger

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Figure 1

Functional remodeling of the rod photoreceptor–to–rod bipolar cell synapse in the retinoschisin-deficient retina.

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Functional remodeling of the rod photoreceptor–to–rod bipolar cell synap...
(A) This schematic shows the synaptic connection between rod photoreceptors (blue, rods) and rod bipolar cells (red, RBC) in the outer retina. For simplicity, all other cell types are shown in gray. (B) Magnified synapse illustrates the differences in organization of the rod-to-rod bipolar cell synapse between WT and synaptically remodeled Rs1–/– mutant retinae (right). In the Rs1–/– animals, the presynaptic structure of the rod is intact, although the intracellular calcium channel concentration and the vGluT1 expression are decreased, suggesting lower abundance of synaptic vesicles and reduced glutamate release. Note that the density of mGluR6 in the postsynaptic Rs1–/– RBC resembles that in the WT RBC, whereas G protein and TRPM1 channel expression at the dendritic tip are reduced.