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.
|Original language||English (US)|
|Number of pages||5|
|Journal||Biochemical and Biophysical Research Communications|
|State||Published - Sep 5 2008|
Bibliographical noteFunding Information:
We gratefully acknowledge the kind gift of R28 cells from Dr. Gail Seigel. This work was supported by EYRO113421 to D.J.T., NIH R01AG025500, NSF CHE-0555341 and American Heart Association 0750115Z to D.H.H.
- Cobalt Chloride (CoCl)
- Gap junctions
- Retinal degeneration