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Effect and Mechanism of Phosphodiesterase Inhibitors on Trabecular Outflow

Korean Journal of Ophthalmology 2019년 33권 5호 p.414 ~ 421
 ( Kim Jae-Woo ) - Catholic University of Daegu School of Medicine Department of Ophthalmology

 ( Lee Jong-Been ) - Catholic University of Daegu School of Medicine Department of Ophthalmology
 ( Lee So-Hyung ) - Catholic University of Daegu School of Medicine Department of Ophthalmology

Abstract


Purpose: Phosphodiesterase (PDE) inhibitors increase matrix metalloproteinase (MMP) production by inhibiting re-uptake of adenosine and may potentiate nitric oxide (NO) activity. This study was performed to investigate the effects and mechanisms of PDE inhibitors on trabecular outflow in cultured human trabecular meshwork cells (HTMCs).

Methods: Primary HTMC cultures were exposed to 0, 20, and 50 μM dipyridamole (DPD) or theophylline (TPN). Permeability through the HTMC monolayer was assessed using carboxyfluorescein. The production of NO was assessed using the Griess assay and MMP-2 levels were measured via Western blotting.

Results: DPD significantly increased permeability accompanied with increased nitrite concentration and MMP-2 levels (all p < 0.05). TPN increased nitrite but did not affect permeability or MMP-2 levels significantly (p > 0.05). When treated with DPD and TPN together, both permeability and nitrite production were increased; however, MMP-2 levels showed no difference compared to DPD exposure alone (p > 0.05).

Conclusions: DPD increased trabecular permeability accompanied with increased nitrite production and MMP-2 levels. PDE inhibitors may increase trabecular outflow by increasing MMP-2 levels and by potentiating NO activity through cyclic GMP in HTMC.

키워드

Dipyridamole; Matrix metalloproteinases; Nitric oxide; Theophylline; Trabecular meshwork
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