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New pharmacological agents for treating glaucoma may be in the offing after researchers have shown that a renin-angiotensin system (RAS) regulates secretion of intracellular fluid in cells from the non-pigmented ciliary body.
The researchers showed that angiotensinogen and AT1b receptor were expressed in human non-pigmented epithelial (HNPE) cells. The cells responded to extracellular angiotensin II with increased intracellular calcium ion concentration. This activated a large conductance potassium ion (BK) channel in the cell membrane, resulting in excretion of potassium ions and intracellular fluid, and a resulting drop in cell volume.
Applying AT1 receptor antagonist losartan extracellularly inhibited this sequence, and intracellular calcium and potassium ion channel activity were unchanged.
PCR and reverse transcriptase PCR were applied to cultured HNPE cells to identify the RAS components AT1 receptor and angiotensinogen. Spectrofluorescence imaging microscopy was used to measure intracellular calcium concentration and cell volume. Single channel patch clamping and whole cell current voltage analysis were used to monitor ion channel activity.
Preliminary indications have suggested that RAS may regulate aqueous humour through its ability to regulate vascular tone in the eye, but not directly by receptor activated signal transduction and ion secretion, as shown in this study.
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