ION AND WATER TRANSPORT IN CILIARY EPITHELIUM

睫状上皮中的离子和水传输

• 批准号: 6329503
• 负责人: NASSER A FARAHBAKHSH
• 金额: $ 29.45万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-09-30 至 2003-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6329503
• 关键词: G protein; biological signal transduction; calcium; calcium channel; calcium flux; electrophysiology; epithelium; eye pharmacology; fluorescence; hormone regulation /control mechanism; intracellular transport; intraocular aqueous flow; ion transport; laboratory rabbit; membrane channels; neurotransmitter metabolism; second messengers; tissue /cell culture; uvea ciliary body; voltage /patch clamp

DESCRIPTION: The eye relies on the aqueous humor for nutrition of the cornea, lens, vitreous and trabecular meshwork, as well as the removal of the waste products of metabolism from these tissues. Steady formation and discharge of the aqueous maintains the intraocular pressure and the optical shape of the eye. A number of drugs commonly used in the treatment of glaucoma lower the intraocular pressure by suppressing the rate of aqueous formation. The ciliary body epithelium is responsible for the formation of aqueous humor and is the target of these drugs. The objective of this project is to characterize in detail the pharmacology and physiology of drug-induced responses and increases in second messengers activity in this epithelium. The PI is particularly interested in the role of Ca2+. The previous studies on intact ciliary body epithelium and on dissociated epithelial cells have shown that many neurotransmitters and hormones act on the cells of ciliary body by increasing the intracellular free Ca2+ concentration. He will use fluorescence ratio imaging on intact as well as dissociated cells to investigate the pharmacology and physiology of the Ca2+ rise in some detail. He will use intracellular recording on intact tissue and patch-clamp recording on dissociated cells to identify influx pathways for Ca2+,as well as other conductive pathways involved in intracellular Ca2+ increase. He will then attempt to identify and characterize the ion channels and transporters modulated by the Ca2+ rise. The PI hope is that he can identify mechanisms involved in the modulation of intracellular Ca2+ concentration and aqueous formation, which may provide new tools for clinical intervention.

描述：眼睛依靠水性幽默来营养 角膜，镜头，玻璃体和小梁网，以及去除 这些组织的新陈代谢的废物产物。 稳定的形成和 水的排放保持眼内压力和光学 眼睛的形状。 用于治疗的许多药物 青光眼通过抑制水性速率来降低眼内压 形成。 睫状体上皮负责形成 幽默是这些药物的靶标。 该项目的目的是详细描述药理学 以及第二使者的药物诱导的反应和增加的生理学 该上皮的活性。 PI对角色特别感兴趣 Ca2+。 先前关于完整睫状体上皮和上的研究 解离的上皮细胞表明许多神经递质和 激素作用于睫状体细胞上的细胞内细胞内 游离Ca2+浓度。 他将使用完整的荧光比成像 以及分解的细胞以研究药理学和生理学 CA2+详细介绍。 他将使用细胞内记录 完整的组织和斑块夹在解离细胞上记录以识别 CA2+的涌入途径以及涉及的其他导电途径 细胞内Ca2+增加。 然后，他将尝试识别和 表征由Ca2+上升调节的离子通道和转运蛋白。 PI希望是他可以确定与调制有关的机制 细胞内Ca2+浓度和水性形成，可能提供 用于临床干预的新工具。