ANIMAL MODEL FOR THE CIRCADIAN RHYTHM OF IOP

IOP 昼夜节律的动物模型

• 批准号: 3259832
• 负责人: DOUGLAS S GREGORY
• 金额: $ 26.48万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-08-01 至 1996-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3259832
• 关键词: adenylate cyclase; alpha adrenergic receptor; beta adrenergic receptor; biological models; catecholamines; circadian rhythms; cyclic AMP; cyclic GMP; fluoresceins; forskolin; indoleamine; inhibitor /antagonist; inositol phosphates; intraocular aqueous flow; intraocular fluid; intraocular pressure; laboratory rabbit; melatonin; norepinephrine; peptide hormone; protein kinase; radiotracer; statistics /biometry; stimulant /agonist; superior cervical ganglion; uvea ciliary body

The long term goal of the work proposed in this application is to understand how IOP and the rate of aqueous flow are regulated. The model to be used to further this goal is the circadian rhythm of IOP and aqueous flow in New Zealand White Rabbits. The goal of the experiments proposed is to identify the receptors, transmitters, and second messengers which mediate the circadian rhythms of IOP and aqueous flow in this animal model. The specific aims of this proposal are: 1.to determine whether norepinephrine and specific beta-adrenergic agonists increase aqueous flow, 2. to determine whether alpha1- or alpha2-adrenergic receptors participate in controlling the. circadian rhythms of IOP and aqueous flow, 3. to measure the aqueous concentrations of transmitters and hormones which are potential mediators of the rhythms of IOP and aqueous flow, 4. to determine the role of cAMP, cGMP and IP3 in mediating the circadian rhythms of IOP and aqueous flow, 5. to determine whether the responsiveness of hormone receptors linked to cAMP, cGMP or IP3 production vary during the circadian cycle, 6. to determine the mechanism of the direct effect of light on TOP during the dark phase of the circadian cycle, 7. to seek evidence for an ocular "clock" which participates in circadian control of IOP and flow in rabbits, 8. to further explore the possibility that melatonin, or other indoleamines, participate in control of the circadian rhythms of IOP and flow. Careful study of the temporal changes of IOP and aqueous flow in this animal model offers a unique opportunity to resolve some of the dilemmas which plague the field of aqueous dynamics. Elucidation of the endogenous mechanisms which control IOP and flow in this animal model is likely to advance our understanding of aqueous dynamics in humans and permit exploitation and manipulation of endogenous regulatory mechanisms in humans to achieve better control of elevated IOP in glaucoma patients.

本申请中提出的工作的长期目标是 了解如何调节IOP和水流速率。 模型 用于进一步的目标是IOP和 新西兰白兔子的水流。 实验的目标 提出的是识别受体，发射器和第二 介导IOP和水流的昼夜节律的使者 这个动物模型。 该提案的具体目的是：1。确定是否是否 去甲肾上腺素和特定的β-肾上腺素能激动剂增加水性 流量，2。确定α1-或α2-肾上腺素能受体是 参与控制。 IOP和水的昼夜节律 流量，3。测量发射机的水浓度和 激素是IOP和水性节奏的潜在介体 流，4。确定CAMP，CGMP和IP3在中介中的作用 IOP和水流的昼夜节律，5。 与CAMP，CGMP或IP3相关的激素受体的反应性 生产在昼夜节车周期中有所不同，6。 光在黑暗阶段的直接效果 昼夜节车周期，7。寻求有关眼的“时钟”的证据 参与兔子的昼夜节律控制，兔子8。 进一步探讨褪黑激素或其他吲哚胺的可能性 参与控制IOP和流动的昼夜节律。 仔细研究IOP和水流的时间变化 在这种动物模型中，提供了一个独特的机会来解决一些 困扰水性动力学领域的困境。 阐明 控制该动物模型中IOP和流动的内源性机制是 可能会促进我们对人类水性动力学的理解和 允许剥削和操纵内源性调节机制 在人类中，可以更好地控制青光眼患者的IOP升高。