May 2006
Volume 47, Issue 13
ARVO Annual Meeting Abstract  |   May 2006
Screening of Gap Junction Antagonists
Author Affiliations & Notes
  • F. Pan
    Ophthalmology, Univ, Houston, TX
  • S.L. Mills
    Ophthalmology, Univ, Houston, TX
  • S.C. Massey
    Ophthalmology, Univ, Houston, TX
  • Footnotes
    Commercial Relationships  F. Pan, None; S.L. Mills, None; S.C. Massey, None.
  • Footnotes
    Support  NIH EY 06515; Vision Core Grant EY 10608; RPB
Investigative Ophthalmology & Visual Science May 2006, Vol.47, 5389. doi:
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      F. Pan, S.L. Mills, S.C. Massey; Screening of Gap Junction Antagonists . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5389.

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

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Purpose: : Many cell types in the retina are coupled via gap junctions. There is a pressing need for a potent and reversible gap junction antagonist. Carbenoxolone is slow, inhibits voltage gated calcium channels and blocks synaptic transmission (Vessey at al., 2004). A series of potential gap junction antagonists was screened by evaluating their effect on dye coupling.

Methods: : Compounds to be tested include: retinoic acid, 18–α–glycyrrhetinic acid, mefloquine, flufenamic acid, meclofenamic acid, niflumic acid and carbenoxolone on the networks of A– and B–type horizontal cells, B–type horizontal cell axon terminals, AII amacrine cells and AII/ON bipolar cells. All cells were injected with 4% Neurobiotin and 1% Lucifer Yellow in DAPI labeled isolated rabbit retina. The efficacy of each drug was determined by measuring the diffusion coefficient for Neurobiotin in the coupled network (Mills and Massey, 1998).

Results: : Mefloquine and meclofenamic acid were the most effective at blocking A–type horizontal cell coupling. Both were effective at a concentration of 200µM. When gap junctions were blocked, single dye–filled horizontal cells were obtained. Niflumic acid and flufenamic acid were less potent. Carbenoxolone was effective at 400µM but may be harmful because the retina seemed opaque and swollen. Mefloquine and meclofenamic acid can also block B–type horizontal cells and AII coupling.

Conclusions: : Mefloquine and meclofenamic acid were both more potent gap junction antagonists than carbenoxolone. They may be potentially useful compounds to manipulate gap junction coupling in retinal networks.

Keywords: horizontal cells • gap junctions/coupling • retina: distal (photoreceptors, horizontal cells, bipolar cells) 

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