June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Physiological Response of RD Mouse Retinal Ganglion Cells to Electrical Stimulation
Author Affiliations & Notes
  • Alice Cho
    Biomedical Engineering, University of Southern California, Los Angeles, CA
  • Alapakkam Sampath
    Biomedical Engineering, University of Southern California, Los Angeles, CA
    Physiology and Biophysics, University of Southern California, Los Angeles, CA
  • Mark Humayun
    Biomedical Engineering, University of Southern California, Los Angeles, CA
    Ophthalmology, University of Southern California, Los Angeles, CA
  • James Weiland
    Biomedical Engineering, University of Southern California, Los Angeles, CA
    Ophthalmology, University of Southern California, Los Angeles, CA
  • Footnotes
    Commercial Relationships Alice Cho, None; Alapakkam Sampath, None; Mark Humayun, Bausch & Lomb (F), Bausch & Lomb (C), Bausch & Lomb (P), Bausch & Lomb (R), Bausch & Lomb (S), Alcon (C), Alcon (R), Iridex (P), Iridex (R), Replenish (I), Replenish (C), Replenish (R), Replenish (S), Second Sight (F), Second Sight (I), Second Sight (C), Second Sight (P), Second Sight (R), Second Sight (S), Regenerative Patch Technologies (I), Regenerative Patch Technologies (C); James Weiland, Second Sight Medical Products, Inc. (F)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 1035. doi:
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    • Get Citation

      Alice Cho, Alapakkam Sampath, Mark Humayun, James Weiland; Physiological Response of RD Mouse Retinal Ganglion Cells to Electrical Stimulation. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1035.

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

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Abstract

Purpose: The aim of this study was to assess how the intrinsic properties of retinal ganglion cells (RGC) in a mouse model of retinal degeneration affect thresholds to electrical stimulation.

Methods: The animal model used for this study was the rd10 mouse, aged 6-10 weeks. The rd10 mutation is caused by a missense mutation on the gene encoding the PDE-β subunit and results in almost complete loss of photoreceptors by the end of two months. Spontaneous baseline activity and spikes elicited by external stimulation were recorded from RGCs using whole-cell patch clamp. The stimulating electrode was a 75 μm diameter Pt-Ir disk positioned approximately 50 μm above and 50 μm laterally from the targeted RGC; the ground electrode was positioned behind the retina on the photoreceptor side. Charge-balanced biphasic square pulses (cathodic-phase first, 500 μs/phase) were delivered at 10 Hz frequency.

Results: For each ganglion cell, measurements for threshold, soma diameter, resting membrane potential, spontaneous firing rate, and presence/absence of rebound excitation were recorded. Since a subset of rd10 RGCs exhibited a high rate of spontaneous activity that was not observed in wildtype mice, cells were classified into two groups - low rate (spontaneous rate < 10 Hz) and high rate (spontaneous rate ≥ 10 Hz) - based on their baseline activity. RGCs with high spontaneous rates had significantly lower electrical thresholds than cells with lower spontaneous rates (μlow = 46.66 μA, μhigh = 27.67 μA, p = 0.0423); the relationships between threshold/resting membrane potential and spontaneous rate were not significant. RGCs were also functionally classified into ON or OFF cells based on their ability to exhibit rebound excitation (D.J. Margolis, 2007). OFF ganglion cells had higher spontaneous firing rates than ON ganglion cells (μOFF = 4.93 Hz, μON = 0.238 Hz, p = 0.0114) but their threshold and resting potential measurements were not statistically different.

Conclusions: OFF ganglion cells appear to exhibit higher rates of spontaneous activity compared to ON ganglion cells and RGCs with higher spontaneous rates had lower electrical thresholds than cells with lower rates. These results suggest that intrinsic spontaneous activity may increase sensitivity to extracellular stimulation and may enable OFF RGCs to be selectively stimulated at lower thresholds than ON RGCs due to their elevated spontaneous firing rates.

Keywords: 508 electrophysiology: non-clinical • 696 retinal degenerations: hereditary  
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