Effect of trans-resveratrol on dexamethasone-induced changes in the expression of MMPs by human trabecular meshwork cells: Involvement of adenosine A1 receptors and NFkB

Intraocular pressure (IOP) lowering in glaucomatous eyes is currently achieved mainly by improved aqueous outflow via alternate drainage pathways. However, the focus is now shifting to trabecular meshwork (TM), the site or major pathological changes including increased extracellular matrix (ECM) deposition and reduced matrix metalloproteinases (MMPs) secretion by TM cells. Trans-resveratrol was previously shown to lower IOP and reduce ECM deposition; however, the mechanisms of action remain unclear. Therefore, we determined the effect of trans-resveratrol on MMP-2 and -9 expression by human TM cells (HTMCs) in the presence of dexamethasone and whether it also affects adenosine A(1) receptors (A(1)AR) expression and nuclear factor kappa B (NFkB) activation. We observed that trans-resveratrol, 12.5 mu M, increased MMP-2 and-9 protein expression by HTMCs despite exposure to dexamethasone (1.89- and 1.53-fold, respectively; P < 0.001). Further it was observed that trans-resveratrol increases A(1)AR expression in HTMC in the presence of dexamethasone (1.55-fold; P < 0.01). Trans-resveratrol also increased NFkB activation in the presence of dexamethasone and A(1)AR antagonist (P < 0.01 versus dexamethasone group). These effects of trans-resveratrol were associated with increased MMP-2 and -9 expression. It could be concluded that trans-resveratrol prevents dexamethasone-induced reduction in MMP-2 and-9 secretion by NFkB activation in HTMCs. This effect of trans-resveratrol is likely to involve increased A(1)AR expression.