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Abstract #8192 Published in IGR 4-3
Adenosine A1 receptor modulation of MMP-2 secretion by trabecular meshwork cells
Shearer TW; Crosson CEInvestigative Ophthalmology and Visual Science 2002; 43: 3016-3020
PURPOSE: Studies have shown that adenosine A1 agonists can lower IOP in rabbits, mice, and monkeys, and this response is mediated in part by increases in outflow facility. The purpose of this project was to evaluate the response of trabecular meshwork cells to the addition of the adenosine A1 receptor agonist N6-cyclohexyladenosine (CHA). METHODS: The human trabecular meshwork (HTM-3) cell line and primary cultures of bovine trabecular meshwork (BTM) cells were used in these studies. Cells were treated with CHA, and the secretion of matrix metalloproteinase (MMP)-2 or the activation of extracellular signal-regulated kinase (ERK1/2) was determined. RESULTS: Treatment of HTM-3 and BTM cells with CHA (0.1 μm) resulted in a time-dependent secretion of MMP-2 that was measurable as early as 30 minutes after treatment and reached a maximum by two hours. This CHA-induced secretion of MMP-2 was inhibited by the adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine (CPT) and by the ERK1/2 pathway inhibitor U0126. Treatment of HTM-3 cells with CHA produced a rapid dose-dependent activation of ERK1/2 with an EC(50) of 5.7 nm. The CHA-induced activation of ERK1/2 was inhibited by pretreatment with the adenosine A1 antagonist CPT and by the ERK pathway inhibitor U0126. CONCLUSIONS: The addition of the adenosine A1 agonist CHA stimulates the secretion of MMP-2 from trabecular meshwork cells. This secretory response involves the activation of adenosine A1-linked stimulation of ERK1/2. These results provide evidence for the existence of functional adenosine A1 receptors in the trabecular cells and that the activation of these receptors stimulates secretion of MMP-2.
T.W. Shearer, MD, Hewitt Laboratory of the Ola B. Williams Glaucoma Center, Department of Ophthalmology, Medical University of South Carolina, Charleston, SC, USA
Classification:
2.5 Meshwork (Part of: 2 Anatomical structures in glaucoma)
3 Laboratory methods
5 Experimental glaucoma; animal models
