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T Yorio, X Zhang, R Krishnamoorthy, G Prasanna, S Narayan; Dexamethasone Endothelin-1 Interactions In Human Non-pigmented Ciliary Epithelial Cells . Invest. Ophthalmol. Vis. Sci. 2002;43(13):4076.
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Purpose: Glucocorticoids increase the intraocular pressure often in individuals susceptible to primary open-angle glaucoma. Endothelin-1 (ET-1) is also implicated in glaucoma as its concentration is elevated in glaucoma patients and in animal models of glaucoma. Currently, the interaction of endothelin with glucocorticoids was determined in human non-pigmented ciliary epithelial cells (HNPE) Methods: Cultured simian virus 40-transformed human NPE (tHNPE) cells were treated with dexamethasone (Dex) 1 nM, 10 nM and 100 nM in serum-free DMEM for 24 hours. ET-1 expression was determined by RT-PCR and ET-1 release was measured by radioimmunoassay. ET receptor expression was determined by RT-PCR, receptor protein expression was measured by western blotting and receptor number was determinded by radioligand binding. Results: Dexamethasone increased ET-1 release in a dose-depended manner and this response was blocked by treatment with RU486, an antagonist of glucocorticoid receptor. Dex also up-regulated ETB, but down-regulated ETA synthesis in this cell line. Binding experiment showed there was a tremendous increase in ETB receptor number after treatment with Dex 10 nM. Conclusion: These studies demonstrate that dexamethasone, a frequently used anti-inflammatory steroid, up-regulates synthesis and release of ET-1 and also regulate its receptors in tHNPE cells. This increase in ET-1 could promote interactions with the mechanism of both inflow and outflow, thus affecting aqueous humor dynamics in the anterior chamber of the eye.
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