Effect of Infliximab on Tumor Necrosis Factor-Alpha-Induced Alterations in Retinal Microvascular Endothelial Cells and Retinal Pigment Epithelial Cells

Purpose: Tumor necrosis factor-alpha (TNF-alpha) may disrupt the extracellular matrix components comprising the blood-retinal barrier (BRB) in patients with posterior uveitis, such as Behcet's disease. We investigated changes in the mRNA expression levels of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in human BRB cells in the presence of TNF-alpha in vitro and examined the effect of infliximab addition. Methods: Cells were cultured in the presence or absence of TNF-alpha, and TNF-alpha-exposed cells were treated with or without infliximab. We measured the expression levels of MMP-1, MMP-2, MMP-3, MMP-9, TIMP-1, and TIMP-2 mRNA in human retinal microvascular endothelial ACBRI181 cells and retinal pigment epithelial ARPE-19 cells by real-time polymerase chain reaction. The cell-derived proteins degraded by MMP were observed after sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Results: Expression of MMP-3 increased and TIMP-1 decreased in the presence of 10 ng/mL TNF-alpha in ACBRI181 cells. Expression of MMP-1 increased and TIMP-2 decreased in the presence of 10 ng/mL TNF-alpha in ARPE-19 cells. These altered levels of expression were reversed by the addition of infliximab. The cell-derived proteins degraded by MMP-1 and -3 were detected in each set of cells. Conclusions: The presence of TNF-alpha altered expression of MMPs and TIMPs in cells comprising the BRB, and infliximab counteracted this alteration.