June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Dependence of Flupirtine-resistant RGC oscillation in deafferentated mouse retinas on Connexin 36
Author Affiliations & Notes
  • Ching-Kang Jason Chen
    Ophthalmology, Baylor College of Medicine, Houston, Texas, United States
    Neuroscience, Baylor College of Medicine, Houston, Texas, United States
  • Yu-Jiun Chen
    Ophthalmology, Baylor College of Medicine, Houston, Texas, United States
  • Yu-Hsu Chen
    Ophthalmology, Baylor College of Medicine, Houston, Texas, United States
  • Chih-Chun Hsu
    Neuroscience, Baylor College of Medicine, Houston, Texas, United States
  • Hung-Ya Tu
    Ophthalmology, Baylor College of Medicine, Houston, Texas, United States
  • Footnotes
    Commercial Relationships   Ching-Kang Chen, None; Yu-Jiun Chen, None; Yu-Hsu Chen, None; Chih-Chun Hsu, None; Hung-Ya Tu, None
  • Footnotes
    Support  NIH Grants EY013811, EY022228, EY002520, unrestrcted grant from Research to Prevent Blindness, Retina Research Foundation
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 2582. doi:
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      Ching-Kang Jason Chen, Yu-Jiun Chen, Yu-Hsu Chen, Chih-Chun Hsu, Hung-Ya Tu; Dependence of Flupirtine-resistant RGC oscillation in deafferentated mouse retinas on Connexin 36. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2582.

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

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Abstract

Purpose : We showed recently by recording from cholinergic amacrine cells that in addition to the AII-amacrine cells (AII-AC) and ON-cone bipolar cells (ONCB) gap junction network, a Flupirtine-resistant oscillation mechanism exists in deafferentated mouse retinas (Front. Cell Neurosci. 9:513). The purposes of the study are to determine 1) the extent at which this novel mechanism drives retinal ganglion cell (RGC) oscillation and 2) whether the two prominent retinal connexins, Cx36 and Cx45, play any role.

Methods : Paired patch-clamp recordings were used to randomly survey 250 RGCs in the Nob mouse background for oscillating membrane potentials and their sensitivity to 15 uM Flupirtine. We used Fast Fourier Transform (FFT) to investigate if and whether a dominant oscillation frequency exists and to calculate the inhibition index (II) whereby sensitivity of oscillation to Flupirtine is defined. Some Nob mice were bred into the Cx36 knockout or the Cx45 conditional knockout background and the degree at which RGC oscillation occurred therein was examined. We used biocytin and Lucifer Yellow in the internal solution to allow recovery of RGC dendritic morphology through post hoc immunohistochemistry and confocal microscopy. Voltage-dependent RGC intrinsic membrane properties were collected to facilitate cell type classification.

Results : The majority of recorded RGCs showed robust membrane potential oscillation but ~14% lacked such heitghtened activity. More than half of oscillating RGCs (~54%) ceased oscillation in the presence of Flupirtine, while ~9 % were completely resistant. Flupirtine treatment dampened oscillation of the rest ~23% of oscillating RGCs and to varying degrees. Consistent with the reported inhibition of Flupirtine-resistant OFF-SAC oscillation by the gap junction blocker meclofenamic acid (MFA), we found both ON- and OFF-SAC oscillation in Nob retinas to be absent when Cx36 but not Cx45 is genetically removed. A further random survey of 200 RGCs in the Nob/Cx36-/- double mutant mice found no oscillating RGCs.

Conclusions : These results demonstrated for the first time that the novel Flupirtine-resistant mechanism can exclusively drive certain RGC types to oscillate aindependent of the prominent AII-AC/ONCB mechanism and that Cx36 is needed for this novel mechanism. Cx45, another abundant retinal connexin, appears to have little/no role in RGC and SAC oscillation in the Nob mice.

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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