June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Single cell electrophysiological assessment of RS1-/Y mice, a model for X-linked retinoschisis
Author Affiliations & Notes
  • Botir T Sagdullaev
    Ophthalmology, Weill Cornell Medicine, New York, New York, United States
    Burke Medical Research Institute, White Plains, New York, United States
  • Elena Ivanova
    Ophthalmology, Weill Cornell Medicine, New York, New York, United States
    Burke Medical Research Institute, White Plains, New York, United States
  • Yang Liu
    Regeneron Pharmaceuticals, Tarrytown, New York, United States
  • Carl Romano
    Regeneron Pharmaceuticals, Tarrytown, New York, United States
  • Footnotes
    Commercial Relationships   Botir Sagdullaev, Regeneron Pharmaceuticals (F); Elena Ivanova, Regeneron Pharmaceuticals (F); Yang Liu, Regeneron Pharmaceuticals (E); Carl Romano, Regeneron Pharmaceuticals (E)
  • Footnotes
    Support  Regeneron Pharmaceuticals
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 280. doi:
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    • Get Citation

      Botir T Sagdullaev, Elena Ivanova, Yang Liu, Carl Romano; Single cell electrophysiological assessment of RS1-/Y mice, a model for X-linked retinoschisis. Invest. Ophthalmol. Vis. Sci. 2017;58(8):280.

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

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Abstract

Purpose : X-linked retinoschisis (XLRS), is an inherited eye disease that causes splitting of the inner retina and loss of visual acuity. Retinoschisis results from mutations in the retinoschisin (RS1) gene which codes for a protein of poorly understood function that is secreted by photoreceptors. Mice lacking this gene recapitulate the structural and electroretinogram (ERG) abnormalities characteristic of the disease. The purpose of this study was to characterize cellular physiology and pathology in mice lacking RS1 using single cell recording techniques.

Methods : The creation and molecular, structural and ERG characterization of the RS1-/Y mice are provided elsewhere in this meeting. Single-cell spiking activity, excitatory and inhibitory postsynaptic currents were recorded from identified retinal ganglion cells (RGCs) in RS1-/Y and age-matched wildtype wholemount retinas. To determine the light sensitivity of the visual output the retinas were probed with spots of light. RGCs were then infused with fluorescent dyes for phenotyping using a Nikon C1 confocal microscope. Fourier analysis was used to determine the dominant frequency component and levels of neuronal activity.

Results : The RGCs in RS1-/Y retinas exhibited elevated rates of spontaneous activity compared to matching RGCs classes in wildtype retinas. Both excitatory and inhibitory current inputs to RGCs were elevated in RS1-/Y retinas suggesting presynaptic origin of the aberrant activity. When probed with light, elevated spontaneous activity masked light evoked responses reducing discrimination of visual output in RS1-/Y retina.

Conclusions : The aberrant neuronal activity in RS1-/Y RGCs represents a functional phenotype of retinoschisis. Elevated spontaneous activity exacerbates the visual impairment, as it obscures discrimination of visual signals. This emerging aberrant activity can serve as a marker for retinal dysfunction in retinoschisis as well as a therapeutic target for functional repair.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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