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Yen Hoong Ooi, Dong-Jin Oh, Douglas J. Rhee; Analysis of α2-adrenergic Receptors and Effect of Brimonidine on Matrix Metalloproteinases and Their Inhibitors in Human Ciliary Body. Invest. Ophthalmol. Vis. Sci. 2009;50(9):4237-4243. doi: 10.1167/iovs.08-2312.
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purpose. To ascertain the expression pattern of α2-adrenergic receptors in the ciliary body (CB) and determine the effect of brimonidine on matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in ciliary body smooth muscle (CBSM) cells.
methods. Qualitative RT-PCR was performed to detect the mRNA of the α2-adrenergic receptor subtypes α2A, α2B, and α2C in CB and CBSM cultures. Immunohistochemistry and immunoblot analysis were performed to further investigate α2A receptor expression in CB tissue and CBSM cells. CBSM cells from 15 different human donors received control or brimonidine tartrate (45 nM) for 1, 3, or 7 days. Changes in pro-MMP-1, -2, -3, -9, and -24 and TIMP-1, -2, -3, and -4 levels were evaluated by Western blot, with GAPDH as the endogenous control. Zymography was used to assess the activity of MMP-1, -2, -3, and -9.
results. The mRNA of α2A, α2B, and α2C were detected in CB tissue and CBSM cells. Immunohistochemistry localized α2A receptors within the CB stroma. Immunoblot analysis demonstrated production by CBSM cells. Brimonidine increased pro-MMP-9 an average of 116% ± 34% (P = 0.0360); enzymatic activity of MMP-9 was unchanged. TIMP-4 decreased an average of 25% ± 8% (P = 0.0329) in conditioned medium, but increased 70% ± 13% (P = 0.0057) in cell lysates.
conclusions. The presence of α2A, α2B, and α2C in CB tissue and CBSM cells indicates the possibility that brimonidine affects uveoscleral outflow. However, the changes in MMP-9 and TIMP-4 without significant changes in MMP-9 activity suggest that a role of the MMP/TIMP system in outflow is unlikely.
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