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Article
Protection of Retinal Cells from Ischemia by a Novel Gap Junction Inhibitor
Biochemical and Biophysical Research Communications (2008)
  • Satyabrata Das, Kansas State University
  • Dingo Lin, Kansas State University
  • Snehalata Jena, Kansas State University
  • Aibin Shi, Kansas State University
  • Srinivas Battina, Kansas State University
  • Duy H. Hua, Kansas State University
  • Rachel A. Allbaugh, Kansas State University
  • Dolores J. Takemoto, Kansas State University
Abstract

Retinal cells which become ischemic will pass apoptotic signal to adjacent cells, resulting in the spread of damage. This occurs through open gap junctions. A class of novel drugs, based on primaquine (PQ), was tested for binding to connexin 43 using simulated docking studies. A novel drug has been synthesized and tested for inhibition of gap junction activity using R28 neuro-retinal cells in culture. Four drugs were initially compared to mefloquine, a known gap junction inhibitor. The drug with optimal inhibitory activity, PQ1, was tested for inhibition and was found to inhibit dye transfer by 70% at 10 μM. Retinal ischemia was produced in R28 cells using cobalt chloride as a chemical agent. This resulted in activation of caspase-3 which was prevented by PQ1, the gap junction inhibitor. Results demonstrate that novel gap junction inhibitors may provide a means to prevent retinal damage during ischemia.

Keywords
  • Ischemia,
  • Cobalt Chloride (CoCl2),
  • Gap junctions,
  • Retinal degeneration,
  • Hypoxia,
  • Caspase-3,
  • HIF1α,
  • PQ1
Publication Date
September 5, 2008
Citation Information
Satyabrata Das, Dingo Lin, Snehalata Jena, Aibin Shi, et al.. "Protection of Retinal Cells from Ischemia by a Novel Gap Junction Inhibitor" Biochemical and Biophysical Research Communications Vol. 373 Iss. 4 (2008)
Available at: http://works.bepress.com/rachel_allbaugh/7/