Effect of Nitric Oxide on the Expression of Matrix Metalloproteinase and Its Association with Migration of Cultured Trabecular Meshwork Cells
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Purpose: To determine the effect of exogenous nitric oxide (NO) on the migration of trabecular meshwork (TM)cells and its association with expression of matrix metalloproteinases (MMPs). Methods: Primary human TM cells treated with 1 or 10 μM S-nitroso-N-acetyl-penicillamine (SNAP) and examinedfor changes in adherence. TM cells were seeded onto transwell culture inserts, and changes in their migratoryactivity were quantified. Reverse transcription polymerase chain reaction was performed to determinethe relative changes in mRNA expression of MMPs and tissue inhibitor of metalloproteinases (TIMPs). Results: Treatment with SNAP did not significantly suppress TM cell adhesion or migration (p > 0.05). Treatmentof TM cells with 10 μM SNAP decreased expression of MMP-2 and increased expression of membranetype MMP-1 and TIMP-2. Treatment with interleukin-1α triggered MMP-3 expression but did not exert significanteffects on MMP-3 activation in response to SNAP. Conclusions: These data suggest that NO revealed no significant effect on the migration of TM cells becauseNO decreased MMP-2 and increased TIMP-2 expression. Although expression of certain MMPs and TIMPschange in response to NO donors, NO may modulate trabecular outflow by changing the cellular production ofextracellular matrix without having a significant effect on the migration of TM cells.
Abstract
Purpose: To determine the effect of exogenous nitric oxide (NO) on the migration of trabecular meshwork (TM)cells and its association with expression of matrix metalloproteinases (MMPs). Methods: Primary human TM cells treated with 1 or 10 μM S-nitroso-N-acetyl-penicillamine (SNAP) and examinedfor changes in adherence. TM cells were seeded onto transwell culture inserts, and changes in their migratoryactivity were quantified. Reverse transcription polymerase chain reaction was performed to determinethe relative changes in mRNA expression of MMPs and tissue inhibitor of metalloproteinases (TIMPs). Results: Treatment with SNAP did not significantly suppress TM cell adhesion or migration (p > 0.05). Treatmentof TM cells with 10 μM SNAP decreased expression of MMP-2 and increased expression of membranetype MMP-1 and TIMP-2. Treatment with interleukin-1α triggered MMP-3 expression but did not exert significanteffects on MMP-3 activation in response to SNAP. Conclusions: These data suggest that NO revealed no significant effect on the migration of TM cells becauseNO decreased MMP-2 and increased TIMP-2 expression. Although expression of certain MMPs and TIMPschange in response to NO donors, NO may modulate trabecular outflow by changing the cellular production ofextracellular matrix without having a significant effect on the migration of TM cells.
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