PEPTIDE AND PROBE MODULATION OF AQUEOUS DYNAMICS

本提案的目标是：1） 组织化学和免疫组织化学方法的体外定位 眼前节中的各种神经肽和2）眼内神经肽。 不同选择性分子探针对离子型细胞的体外效应 睫状上皮中的事件与体内生理和 这些药物对眼内压的药理作用。 研究将提供有关神经肽作用的信息（低 分子量、生物活性内源性蛋白）和分子探针 （细胞离子运输、交换或通道的化学抑制剂） 作为房水的生理调节剂或药理调节剂 动力学 结果将提供深入了解因素控制 眼内压和正常的房水生理学。 新的和独特 对房水动力学的药理学操作是可能的 有可能证明青光眼的新疗法。 药物诱导的眼内改变的机制 压力将被调查。 流出量的无创测量 设施，巩膜外静脉压和房水流量将 执行。 有创测定房水流量，总流出量 将测量设备和眼血流量和体积。 生化测定包括测量房水蛋白， 抗坏血酸和环AMP浓度。 房水动力学研究 在局部、全身、前房内或玻璃体内 局 待研究的神经肽包括加压素和 神经肽Y注意力集中在确定特异性和 这些药物与传统神经递质的相互作用。 在 此外，在体外研究的影响，神经肽， 将对眼前节平滑肌进行调节/修饰 为了提供关于这些天然存在的肽的额外信息， 荷尔蒙 分子探针阿米洛利（钠转运抑制剂） 和apamin（钾转运抑制剂）将被研究其 对眼内压的影响

The objectives of this proposal are the correlation of 1) the in vitro localization by histochemical and immunohistochemical methods of various neuropeptides in the anterior segment of the eye and 2) the in vitro effects of various selective molecular probes on ionic cellular events in the ciliary epithelium with the in vivo physiological and pharmacological effects of these agents on intraocular pressure. Investigations will provide information on the role of neuropeptides (low molecular weight, bioactive endogenous proteins) and molecular probes (chemical inhibitors of cellular ionic transport, exchange, or channels) as physiologic regulators or pharmacologic modulators of aqueous humor dynamics. Results will provide insights into factors controlling intraocular pressure and normal aqueous humor physiology. New and unique pharmacologic manipulations of aqueous humor dynamics may be possible with the potential for the demonstration of new therapies for glaucoma. Mechanisms responsible for drug-induced alterations in intraocular pressure will be investigated. Noninvasive measurements of outflow facility, episcleral venous pressure and aqueous humor flow will be performed. Invasive determination of aqueous humor flow, total outflow facility, and ocular blood flow and volume, will be measured. Biochemical determinations include measurement of aqueous humor protein, ascorbate, and cyclic AMP concentration. Aqueous humor dynamic studies are performed following topical, systemic, intracameral, or intravitreal administration. Neuropeptides to be investigated include vasopressin and neuropeptide Y. Attention is directed to determining the specificity and the interaction of these agents with classical neurotransmitters. In addition, in vitro studies of the effects of neuropeptides as regulators/modifiers on anterior segment smooth muscles will be performed to provide additional information on these naturally occurring peptide hormones. The molecular probes amiloride (sodium transport inhibitor) and apamin (potassium transport inhibitor) will be investigated for their effect on intraocular pressure.