June 2015
Volume 56, Issue 7
ARVO Annual Meeting Abstract  |   June 2015
Homologous network interactions between AII amacrine cells are essential for aberrant activity in RD
Author Affiliations & Notes
  • Christopher Yee
    Weill Cornell Medical College, New York, NY
  • Elena Ivanova
    Weill Cornell Medical College, New York, NY
  • Botir T Sagdullaev
    Weill Cornell Medical College, New York, NY
  • Footnotes
    Commercial Relationships Christopher Yee, None; Elena Ivanova, None; Botir Sagdullaev, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 3230. doi:
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      Christopher Yee, Elena Ivanova, Botir T Sagdullaev; Homologous network interactions between AII amacrine cells are essential for aberrant activity in RD. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3230.

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

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Purpose: In retinal degeneration (RD), the diminished light signal from dying photoreceptors has been considered to be the sole cause of impairment. Rather, there is a concomitant 10-fold increase in spontaneous activity, evident from early stages of disease, which forms a new barrier for the visual signal by increasing noise in the neuronal network, exacerbating the visual deficit. We showed that reducing this noise by blocking gap junctions improves signal fidelity in RD retina. This intervention targets an aberrant network of gap junction-coupled inner retinal neurons that oscillate to generate noise in RD retina, with AII amacrine cells playing a key role. The purpose of the present study is to address a controversy regarding the respective roles for homologous AII-AII cell coupling versus heterologous AII-ON Cone BC coupling in mediating aberrant activity in RD.

Methods: Intact retinal whole mounts were prepared from rd10/Cx36-/- mice, rd10 mice (P60-250) and age matched controls. Spiking neuronal activity from retinal ganglion cells was monitored in cell attached mode under physiological conditions.

Results: By crossing connexin36 knockout mice (Cx36-/-, provided by Dr. David Paul) with rd10 mice, we generated rd10/Cx36-/- mice, which exhibit retinal degeneration but lack a protein that forms gap junctions, particularly those between adjacent AII amacrine cells. We found that, even in face of aggressive photoreceptor degeneration, oscillatory activity in rd10/Cx36-/- mice was diminished compared to rd10 littermates, providing the first strong evidence for a key role for Cx36-containing gap junctions, which are known to mediate electrical connections among AII cells. However, AII cells can make gap junction connections among each other and with ON cone BC cells. Controversy still remains regarding the role of homologous AII-AII coupling versus heterologous AII-ON cone BC coupling. To further distinguish contribution of these two pathways we selectively blocked gap junction activity between AII-ON cone bipolar cells. We found that aberrant activity persisted following application of the NO-donor SNAP, which closes ON cone BC-AII heterologous connections.

Conclusions: These data suggest that homologous network coupling of AII amacrine cells is essential in mediating aberrant activity in RD.


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