Comparative Study of the Effects of Trabecular Meshwork Outflow Drugs on the Permeability and Nitric Oxide Production in Trabecular Meshwork Cells
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Purpose: To compare the effects of the barrier function in human trabecular meshwork (TM) cells monolayerand the production of nitric oxide (NO) between trabecular outflow drugs, Rho-associated kinase (ROCK) inhibitors,adenosine, and statin. Methods: Primary cultured TM cells were exposed to 10 or 25 mM Y-27632, 0.1 or 1 mM N6-cyclohexyladenosine(CHA), or 15 or 30 mM simvastatin for 24 hours. NO production and expression of endothelial nitric oxidesynthase mRNA were measured by Griess assay and reverse transcription polymerase chain reaction, respectively. Barrier functions of the TM cell monolayer were measured by carboxyfluorescein and trans-endothelialelectrical resistance. The expression of matrix metalloproteinase-2 mRNA was assessed with reversetranscription polymerase chain reaction. Results: In TM cells, treatment with each drug increased endothelial nitric oxide synthase mRNA expression. Treatment with 25 mM Y-27632 and 1.0 mM CHA increased NO production significantly (p = 0.035 and p = 0.043,respectively). Treatment with each drug increased the permeability (all p = 0.001) and decreased the trans-endothelialelectron resistance of the TM cell monolayer. Treatment with 0.1 mM and 1.0 mM CHA significantlyincreased matrix metalloproteinase-2 mRNA expression, but simvastatin inhibited its expression. Conclusions: Since treatment with ROCK inhibitor more greatly increased NO production and permeability thandid adenosine or statin, ROCK inhibitor seems to be more effective for lowering intraocular pressure.
Abstract
Purpose: To compare the effects of the barrier function in human trabecular meshwork (TM) cells monolayerand the production of nitric oxide (NO) between trabecular outflow drugs, Rho-associated kinase (ROCK) inhibitors,adenosine, and statin. Methods: Primary cultured TM cells were exposed to 10 or 25 mM Y-27632, 0.1 or 1 mM N6-cyclohexyladenosine(CHA), or 15 or 30 mM simvastatin for 24 hours. NO production and expression of endothelial nitric oxidesynthase mRNA were measured by Griess assay and reverse transcription polymerase chain reaction, respectively. Barrier functions of the TM cell monolayer were measured by carboxyfluorescein and trans-endothelialelectrical resistance. The expression of matrix metalloproteinase-2 mRNA was assessed with reversetranscription polymerase chain reaction. Results: In TM cells, treatment with each drug increased endothelial nitric oxide synthase mRNA expression. Treatment with 25 mM Y-27632 and 1.0 mM CHA increased NO production significantly (p = 0.035 and p = 0.043,respectively). Treatment with each drug increased the permeability (all p = 0.001) and decreased the trans-endothelialelectron resistance of the TM cell monolayer. Treatment with 0.1 mM and 1.0 mM CHA significantlyincreased matrix metalloproteinase-2 mRNA expression, but simvastatin inhibited its expression. Conclusions: Since treatment with ROCK inhibitor more greatly increased NO production and permeability thandid adenosine or statin, ROCK inhibitor seems to be more effective for lowering intraocular pressure.
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