July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Remodeling in rescued RP retina
Author Affiliations & Notes
  • Susanne Koch
    Physiology, LMU, Munich, Germany
  • Jacqueline Kajtna
    Physiology, LMU, Munich, Germany
  • Stephen Tsang
    Ophthalmology, Columbia University, New York, United States
  • Footnotes
    Commercial Relationships   Susanne Koch, None; Jacqueline Kajtna, None; Stephen Tsang, None
  • Footnotes
    Support  Emmy Noether Grant
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 6065. doi:
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      Susanne Koch, Jacqueline Kajtna, Stephen Tsang; Remodeling in rescued RP retina. Invest. Ophthalmol. Vis. Sci. 2019;60(9):6065.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose : In retinitis pigmentosa (RP) retinas, the characteristic photoreceptor cell death is preceded by several other pathological changes – including changes in retinal circuitry. The impact of these changes for rescue of vision following gene therapy is not known. We analyzed the plasticity of neural circuitry in RP retinas after treatment at mid- and late disease stages.

Methods : Experiments were performed in an RP mouse model (Pde6bSTOP), which contains a floxed STOP cassette in the Pde6b gene. The STOP cassette prevents PDE6b expression and leads to degeneration. What distinguishes this mouse model from other RP mouse models, is the fact that the floxed STOP cassette can be easily removed using Cre – resulting in Pde6b activation, thereby mimicking gene therapy. We used the mice in combination with a tamoxifen-inducible and rod-specific Pde6g::CreERT2 driver and induced rescue at mid- and late-stage disease by tamoxifen injection. We analyzed rescued retinas (vs uninjected mutant and wild type) by immunohistochemistry, electron microscopy, multielectrode array and ERG (N=5).

Results : Pde6bSTOP-retinas undergo structural changes in the inner retina, which lead to changes in electrophysiological function. We observed loss of bipolar processes, bipolar cell body migration into the photoreceptor layer, and dramatic reductions in the number of rod ribbon synapses. Further downstream, retinal ganglion cells (RGCs), whose axons connect the retina to the brain, exhibited numerous electrophysiological changes, eg, increased and rhythmic spontaneous action potential spiking rates. In treated retinas, some of the miswired connections and aberrant electrical signals were reversible. Specifically, the synaptic structure between photoreceptors and their postsynaptic targets returned to normal following rod rescue at mid and late disease time points. ON bipolar cell activity is rescued, and that rescue depends on the time point of treatment (earlier is better).

Conclusions : Circuits in rescued RP retina are plastic, although this capacity to remodel decreases with disease progression. Further structural and functional examinations will be needed to provide a critical knowledge base for designing vision rescue strategies.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.


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