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Sumon Roy, Kyle Trudeau, Rafael Simo, Sayon Roy; Effect of Fenofibric Acid on Fibronectin Overexpression and Barrier Permeability Associated with Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3577.
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Excess synthesis of extracellular matrix (ECM) components, including fibronectin, has been shown to promote vascular permeability in the diabetic retina. Our recent studies indicate that fenofibric acid’s anti-permeability effect on the outer blood retinal barrier (BRB) is linked to its inhibitory effect on ECM overexpression. In this study, we investigated whether fenofibric acid (FA) imparts a beneficial effect on the inner BRB by reducing endothelial cell permeability and whether this involves reduction of fibronectin overexpression.
To determine whether FA reduces high glucose (HG)-induced fibronectin overexpression and increased permeability in rat retinal endothelial cells (RRECs), cells were grown in normal glucose (5 mM) or HG (30 mM) medium for 7 days, and in HG medium exposed to FA (100 µM) for the last 3 days of the study. Western blot analysis was performed to determine the effect of FA on FN protein expression, and in vitro permeability (IVP) assay was performed to assess the effect of FA on cell monolayer permeability.
Western blot analysis showed FN protein expression was significantly increased in RRECs grown in HG medium compared to those grown in normal medium (182 ± 37% of control; p<0.05). When cells grown in HG medium were supplemented with FA, a significant reduction in FN protein expression compared to cells grown in HG medium was observed (121 ± 26% of control; p<0.05). IVP assay indicated significantly increased permeability in cells grown in HG medium compared to cells grown in normal medium (165 ± 41% control; p<0.05). Treatment with FA significantly reduced cell monolayer permeability in cells grown in HG condition (130 ± 17% of control; p<0.05).
Findings from this study suggest that FA’s beneficial effect in protecting against the inner BRB leakage is mediated at least in part through its inhibitory effect on fibronectin overexpression associated with diabetic retinopathy.
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