Trabecular meshwork (TM) cells are now considered to play an active role in the aqueous outflow mechanism, since they exhibit smooth muscle-like contractile properties. Endothelin-1 (ET-1), a potent vasoconstrictor peptide, has been proposed to play a role in the local regulation of aqueous outflow and intraocular pressure (IOP) control. We propose an in vitro culture model as a method in the study of ET-1 induced human trabecular meshwork (HTM) cell contractility and if the pre-incubation with flunarizine, a calcium channel blockers, can inhibit the action of ET-1 . Experiments were performed on semi confluent HTM cells (primary cultures established from normotensive human donor eyes) at the 2nd passage with PBS as control. The contractile status of the cells was evaluated by a morphometric analysis of cell area, assuming that HTM cells in culture are able to reduce their area as a consequence of cytoskeletal contraction rather than regulatory volume decrease After incubation with 10µM ET-1 for 5 minutes we observed a reduction of HTM cell area as respect to PBS treated cells: 2425±876 mm2 vs. 3125±987 mm2 (p<0.001) and cells exhibited a retraction in shape and indented profiles. Administration of ET-1 at progressively lower doses produced a correspondent lower reduction of HTM cell area suggesting a dose-response ET-1 effect. We demonstrated that pre-incubation with 10µM flunarizine strongly inhibited the ET-1 effect on HTM cell contraction: 2806±865 mm2 vs. 2910.±846 mm2. (p= n.s.). Our data would indicate that ET-1 induced HTM cells area reduction statistically significant vs. control and can directly influence the aqueous outflow moreover flunarizine inhibits the ET-1 effect on the HTM cells.

Effects of Endothelin-1 and Flunarizine on human trabecular meshwork cell contraction.

CELLINI, MAURO;VERSURA, PIERA;BENDO, EDLIRA;CAMPOS, EMILIO
2006

Abstract

Trabecular meshwork (TM) cells are now considered to play an active role in the aqueous outflow mechanism, since they exhibit smooth muscle-like contractile properties. Endothelin-1 (ET-1), a potent vasoconstrictor peptide, has been proposed to play a role in the local regulation of aqueous outflow and intraocular pressure (IOP) control. We propose an in vitro culture model as a method in the study of ET-1 induced human trabecular meshwork (HTM) cell contractility and if the pre-incubation with flunarizine, a calcium channel blockers, can inhibit the action of ET-1 . Experiments were performed on semi confluent HTM cells (primary cultures established from normotensive human donor eyes) at the 2nd passage with PBS as control. The contractile status of the cells was evaluated by a morphometric analysis of cell area, assuming that HTM cells in culture are able to reduce their area as a consequence of cytoskeletal contraction rather than regulatory volume decrease After incubation with 10µM ET-1 for 5 minutes we observed a reduction of HTM cell area as respect to PBS treated cells: 2425±876 mm2 vs. 3125±987 mm2 (p<0.001) and cells exhibited a retraction in shape and indented profiles. Administration of ET-1 at progressively lower doses produced a correspondent lower reduction of HTM cell area suggesting a dose-response ET-1 effect. We demonstrated that pre-incubation with 10µM flunarizine strongly inhibited the ET-1 effect on HTM cell contraction: 2806±865 mm2 vs. 2910.±846 mm2. (p= n.s.). Our data would indicate that ET-1 induced HTM cells area reduction statistically significant vs. control and can directly influence the aqueous outflow moreover flunarizine inhibits the ET-1 effect on the HTM cells.
M. CELLINI; P. VERSURA; E. ZAMPARINI; E. BENDO; E.C. CAMPOS
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11585/34917
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