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ABSTRACT: Trabecular meshwork (TM) cells are now considered to play an active role in the aqueous outflow mechanism because 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 for the study of ET-1-induced human TM (HTM) cell contractility and for the study of whether pre-incubation with flunarizine, a calcium-channel blocker, can inhibit the action of ET-1. Experiments were performed on semiconfluent HTM cells (primary cultures established from normotensive human donor eyes) at the second passage, with phosphate-buffered saline (PBS) as a 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 10 microM ET-1 for 5 mins, we observed a reduction of HTM cell area with respect to PBS-treated cells: 2425 +/- 876 microm2 versus 3125 +/- 987 microm2 (P < 0.001); and cells exhibited a retraction in shape and a reduction in number of indented profiles. Administration of ET-1 at progressively lower doses produced a corresponding lower reduction of HTM cell area, suggesting a dose-response effect of ET-1. Pre-incubation with 10 microM flunarizine strongly inhibited the ET-1 effect on HTM cell contraction: 2806 +/- 865 microm2 versus 2910 +/- 846 microm2 (P = not significant). Our data indicate that ET-1 induced a statistically significant reduction in the area of HTM cells versus controls, and that ET-1 can directly influence the aqueous outflow. Moreover, we observed that flunarizine inhibited the effect of ET-1 on the HTM cells.
Experimental Biology and Medicine 07/2006; 231(6):1081-4. · 2.64 Impact Factor
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ABSTRACT: A 73-year-old woman presented with a 2-day history of decreased vision in here right eye. The patient had a history of giant cell arteritis successfully treated 5 years previous to this presentation. She had been off corticosteroids for 3 years. A repeat temporal artery biopsy was positive.
Survey of Ophthalmology 53(3):296-300. · 2.35 Impact Factor
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ABSTRACT: A 58-year-old woman presented with a problem with her peripheral vision. Computed tomography scan showed an occipital hemorrhagic stroke. She subsequently suffered gastrointestinal bleeding and at surgery biopsy of a portion of the middle colic artery aneurysm revealed changes consistent with polyarteritis nodosa.
Survey of Ophthalmology 54(1):128-34. · 2.35 Impact Factor
