| Budget Amount *help |
¥3,880,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥480,000)
Fiscal Year 2007: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
To clarify the vasodilatory mechanism of various antiglaucoma ophthalmic agent, we have investigated the effect of levobunolol and prostaglandin analogs on isolated rabbit ciliary artery in vitro. Under the dissecting microscope, ciliary arteries were prepared from albino rabbit eyes and mounted in a myograph system. The effects of various agents were investigated using isometric tension recording methods. The effects of the same agents on intracellular free calcium ([Ca^<2+>]I) in cultured human aortic smooth muscle cells were also studied by fluorophotometry. Levobunolol relaxed ciliary artery pre-contracted with either high-K solution, 1 μM histamine, 10 μM phenylephrine, or 100 nM endothelin-1. Inhibition of endothelial nitric oxide synthase or denudation of the endothelium did not affect this relaxation. Experimental results indicate that levobunolol may relax rabbit ciliary artery by two different mechanisms. First, the relaxation could be due to the blockade of Ca^<2+> entry thr
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ough non voltage-dependent Ca^<2+> channels. Second, lecobunolol may change the Ca^<21> sensitivity of vascular smooth muscle cells. Tafluprost induced a concentration-dependent relaxation in rabbit ciliary arteries pre-contracted with a high-K solution. Tafluprost was more potent than prostaglandin E_2 (PGE_2) or prostaglandin I_2 (PGI_2). Relaxation of rabbit ciliary artery smooth muscle by tafluprost may be due, at least in part, to inhibition of capacitative Ca^<2+> entry from the extracellular space. Many anti-glaucoma agents have vasodilatory effect on isolated rabbit ciliary artery. These actions may explain the mechanisms of increased ocular blood flow in vivo. However, mechanisms of these drugs in relaxing ciliary artery differ from each other and are also different from that of IOP reduction. Though it is generally accepted that increased intraocular pressure is a major risk factor in glaucoma, ocular vascular perfusion is also important in the pathogenesis of optic nerve damage and visual field loss, especially in patients with normal tension glaucoma. Therefore a better understanding of the effect of various antiglaucoma agents on ocular circulation is important for optimizing their clinical use. Less
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