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Ectopic synaptogenesis in the mammalian retina caused by rod photoreceptor-specific mutations

Nature Neuroscience volume 3, pages 1121–1127 (2000)Cite this article

Abstract

In addition to rod photoreceptor loss, many mutations in rod photoreceptor-specific genes cause degeneration of other neuronal types. Identifying mechanisms of cell–cell interactions initiated by rod-specific mutations and affecting other retinal cells is important for understanding the pathogenesis and progression of retinal degeneration. Here we show in animals with rod and cone degeneration due to mutations in the genes encoding rhodopsin and cGMP phosphodiesterase β-subunit (PDE-β) respectively, that rod bipolar cells received ectopic synapses from cones in the absence of rods. Thus, synaptic plasticity links certain rod-specific mutations to retina-wide structural alterations that involve different types of neurons.

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Figure 1: Cross sections of 10-month-old normal and P347L porcine retinas stained with anti-PKCα antibody using the immunoperoxidase method showed survival of rod bipolar cells and alterations in their dendritic appearance.
Figure 2: Synaptophysin immunoreactivity used for the visualization of surviving cone terminals.
Figure 3: Cross sections of P347L retinas double-immunostained with anti-PKCα antibody (green, FITC) and anti-synaptophysin antibody (red, rhodamine) revealed ectopic synaptic contacts between dendrites of surviving rod bipolar cells and cone terminals.
Figure 4: Two types of contact made by the ectopic cone–rod bipolar cell synapses.
Figure 5: Expression of the Go G protein by rod bipolar cells.
Figure 6: Survival of cones and rod bipolar cells in degenerated rd retinas.
Figure 7: Cross sections of 18-day-old rd retina double-immunostained with anti-PKCα antibody (green, FITC) and anti-synaptophysin antibody (red, rhodamine) revealed ectopic synaptic contacts between dendrites of surviving rod bipolar cells and cone terminals.
Figure 8: Rod bipolar cell dendrites made ectopic flat contacts with cone terminals in degenerated rd retinas.

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Acknowledgements

We thank members of the North Carolina State University Swine Educational Unit for producing the pigs, Bruce Collins and Jeffrey Sommer for genotyping pigs, Ewa Worniallo for assistance with electron microscopy and Paul Hargrave of the University of Florida for the anti-rhodopsin mouse monoclonal antibody. This work was supported by the National Eye Institute (RO1EY11498 and P30EY05722), Foundation Fighting Blindness of Hunt Valley, Maryland and Research to Prevent Blindness of New York, New York.

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Authors and Affiliations

  1. Department of Opthalmology, Duke University School of Medicine, Durham, 27710, North Carolina, USA

    You-Wei Peng, Ying Hao & Fulton Wong

  2. Department of Neurobiology, Duke University School of Medicine, Durham, 27710, North Carolina, USA

    You-Wei Peng & Fulton Wong

  3. Department of Animal Science, North Carolina State University, Raleigh, 27695, North Carolina, USA

    Robert M. Petters

  4. Department of Pathology, Duke University School of Medicine, Durham, 27710, North Carolina, USA

    Fulton Wong

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Correspondence to Fulton Wong.

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Peng, YW., Hao, Y., Petters, R. et al. Ectopic synaptogenesis in the mammalian retina caused by rod photoreceptor-specific mutations. Nat Neurosci 3, 1121–1127 (2000). https://doi.org/10.1038/80639

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