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Z. T. Resch, C. K. Bahler, U. Roy Chowdhury, M. P. Fautsch; Diazoxide Increases Outflow Facility in the Human Anterior Segment Culture Model. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3221. doi: https://doi.org/.
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To determine the effect of diazoxide, a non-specific potassium channel opener, on outflow facility in the human anterior segment culture model.
The anterior segments of human eyes were placed in perfusion organ culture (76 ± 14 years, mean ± SD, n=7). One eye received an anterior chamber exchange with DMEM containing 20 µM diazoxide while the fellow eye received vehicle (DMSO). In two pairs of eyes, one anterior segment received diazoxide (20 µM) while the fellow eye received diazoxide (20 µM) and 5 µM glibenclamide (potassium channel blocker) for up to 48 hours. Drugs were removed and anterior segments were perfused with DMEM for 24 hours. A crossover experiment was performed. The anterior segments that initially received diazoxide alone were treated with diazoxide and glibenclamide while the fellow anterior segments that received diazoxide and glibenclamide were treated with diazoxide alone. Real-time PCR, Western blot, and immunohistochemistry were used to examine the expression of ATP-sensitive potassium channel subunits (Kir6.1, Kir6.2, SUR2A, SUR2B) in human trabecular meshwork tissue and human primary trabecular meshwork monolayer cells.
Anterior segments treated with diazoxide had increased outflow facility when compared to fellow anterior segments treated with vehicle alone (130% ± 65% vs. 2% ± 7%, n=7, p<0.02). Outflow facility returned to near baseline levels within 24 hours of diazoxide removal (n=5, p=0.99). In anterior segment crossover experiments, addition of glibenclamide inhibited diazoxide from increasing outflow facility (diazoxide and glibenclamide 6% ± 17% vs. diazoxide alone 116% ± 70%; n=4). ATP-sensitive potassium channel subunits Kir6.1, Kir6.2, SUR2A and SUR2B were expressed in trabecular meshwork tissue and primary trabecular meshwork monolayer cells.
Diazoxide increases outflow facility in the human anterior segment culture model. Diazoxide may increase outflow facility by affecting ATP-sensitive potassium channel subunits that are expressed in the trabecular meshwork.
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