Contractile Modulation of Distal Aqueous Humor Drainage

项目总结/摘要 研究远端房水引流道及其调节的意义在于， 显著增加了水流出阻力。这种流出阻力是眼内压的主要决定因素 （IOP）。眼压是青光眼的主要危险因素，青光眼是全球不可逆失明的主要原因。我们不 了解IOP是如何调节的。青光眼中IOP失调的原因是什么？ 大部分也是未知的。该项目的长期目标是提高我们对IOP调节的理解， 青光眼的发病机制，并制定更有效的临床治疗。这种改进的疗法应该更好地 以改变青光眼自然病程的方式靶向IOP升高的潜在机制， 否则会导致失明。健康的好处将被视为在更好地保护视力，积极 影响患者的生活。 背景和科学需要。越来越多地进行手术绕过小梁网，以降低 治疗青光眼。一旦高阻力的网状组织 然而，它被绕过了。因此，远端房水引流道必须保持对流出的显著阻力 位于小梁网和下游血管之间。因此，重要的是要了解 远端房水引流道的细胞组织及其对流出阻力的影响，但我们非常了解 很少知道它是如何工作的。这代表了我们科学知识中的一个重要差距，这是一个障碍， 了解和治疗青光眼。 创新我们假设远端房水引流道的壁有收缩的能力， 管道的口径和尺寸这提供了一种调节房水流出阻力和IOP的机制。 我们试图确定远端管道收缩性的分子标志物，并确定它们在调节血管收缩中的作用。 房水流出 我们将通过双光子显微镜来研究各种突变小鼠，该显微镜可以分辨组织内的细胞，以解决突变小鼠的基因突变。 具体目的是：（1）确定远端房水引流道的细胞特征;（2）确定 其中存在收缩机制并通过该途径影响流出。 冲击该项目旨在提高我们对健康和疾病中IOP调节的理解， 治疗青光眼的方法有哪些

PROJECT SUMMARY/ABSTRACT The significance of studying the distal aqueous drainage tract and its regulation is that the tract contributes significantly to aqueous outflow resistance. This outflow resistance is a major determinant of intraocular pressure (IOP). IOP is a key risk factor for glaucoma, the leading cause of irreversible blindness worldwide. We do not understand enough about how IOP is regulated. By what means IOP becomes dysregulated in glaucoma is mostly also unknown. The long-term objective of the project is to improve our understanding of IOP regulation, glaucoma pathogenesis and to develop more effective clinical therapy. Such improved therapy should better target the underlying mechanism of IOP elevation in a way that alters the natural course of glaucoma that would otherwise lead to blindness. The health benefits will be seen in better preservation of vision that positively impacts patients' lives. Background and scientific need. Surgically bypassing the trabecular meshwork is increasingly performed to lower IOP and treat glaucoma. IOP does not fall as far as might be expected once the high resistance meshwork tissue is bypassed, however. Significant resistance to outflow must then remain in the distal aqueous drainage tract situated between the trabecular meshwork and downstream blood vessels. It is thus important to understand the cellular organization of the distal aqueous drainage tract and its effect on outflow resistance, but we know very little about how it works. This represents an important gap in our scientific knowledge that is a barrier to better understanding and treating glaucoma. Innovation. We postulate that walls of the distal aqueous drainage tract have capacity to contract to alter the tract's caliber and dimensions. This provides a mechanism for regulating aqueous outflow resistance and IOP. We seek to identify molecular markers of contractility in the distal tract and determine their role in regulating aqueous humor outflow. We will study various mutant mice by 2-photon microscopy that resolves cells within tissues to address the specific aims to: (1) ascertain cellular characteristics of the distal aqueous drainage tract; (2) determine the extent to which contractile mechanisms are present and affect outflow by this pathway. Impact. The project seeks to improve our understanding of IOP regulation in health and disease and discover more effective ways to treat glaucoma.