Artikel
Purinergic modulation of human Schlemm's canal and trabecular meshwork cells
Suche in Medline nach
Autoren
Veröffentlicht: | 22. September 2004 |
---|
Gliederung
Text
Objective
Adenosine can lower IOP in humans. A1 adenosine receptor (AR) agonists can lower and A2a increase IOP in several species. Main target sites and underlying mechanisms are unknown. Concentrations of aqueous humor adenosine are increased in patients with primary open-angle glaucoma and PEX glaucoma.
Methods
We applied selective AR agonists to human Schlemm's canal cells and a human trabecular meshwork cell line (hTM5) to evaluate the effects on whole-cell current and to determine whether cell volume is altered. Inner-wall SC (IW-SC) cells were isolated by a novel enzyme-assisted technique, followed by cell selection with antibody to the SC-cell marker CD31/PECAM-1. Cells grown on coverslips were loaded with calcein-AM and Pluronic F-127 to measure cell area as an index of cell volume by videomicroscopy. Whole-cell currents were recorded using patch-clamp technique.
Results
The A1AR agonist S-ENBA increased IW-SC whole-cell currents (100nM, 18/22 applications, 718±232%). In contrast the A2AAR agonist CGS 21680 reduced currents (30nM, 4/7, -29±7%). Contrary hTM5 cells responded to all subtype-specific AR agonists tested with increased currents. Only the A1AR agonist S-ENBA shrank the inner-wall SC cells (-2.4±0.1%, N=8) and only the A2AAR agonist CGS 216380 shrank the hTM5 cells (-3.1±0.1%, N=7).
Conclusions
IW-SC cells can be isolated by a novel technique. All AR agonists tested alter inner-wall SC cells as well as hTM5 cells whole-cell current. Opposing actions of A1 and A2a AR agonists on IW-SC whole-cell currents suggest IW-SC may mediate IOP modulation.