Contractile Modulation of Distal Aqueous Humor Drainage

项目摘要/摘要 研究远端房水引流道及其调控的意义在于远端房水引流道对 对水的流出阻力有显著影响。这种流出阻力是眼压的主要决定因素。 (眼压)。眼压是青光眼的关键风险因素，青光眼是全球不可逆转失明的主要原因。我们不会 对眼压如何调节有足够的了解。青光眼患者眼压失调的原因是 大部分也是未知的。该项目的长期目标是提高我们对眼压调节的理解， 以期为青光眼的发病机制及临床治疗提供更有效的方法。这种改进的治疗方法应该会更好 针对潜在的眼压升高机制，改变青光眼的自然病程， 否则会导致失明。对健康的好处将体现在更好地保护视力上， 影响病人的生活。 背景和科学需要。通过手术绕过小梁网状结构，越来越多的手术是为了降低 降眼压和治疗青光眼。一旦高阻网状组织，眼压不会像预期的那样下降 然而，它被绕过了。因此，在远端房水引流管道中必须保持显著的流出阻力 位于小梁网和下游血管之间。因此，重要的是理解 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 对它的工作原理知之甚少。这代表了我们科学知识中的一个重要差距，这是更好地 认识和治疗青光眼。 创新。我们推测远端房水引流道壁有收缩的能力来改变 轨迹的口径和尺寸。这为调节房水流出阻力和眼压提供了一种机制。 我们试图确定远端肌束收缩能力的分子标志物，并确定它们在调节中的作用。 房水流出。 我们将通过双光子显微镜研究各种突变的小鼠，这种显微镜可以分解组织内的细胞，以解决 具体目的：(1)确定远端房水引流道的细胞特征；(2)确定引流管的范围 存在收缩机制，并通过这一途径影响外流。 冲击力。该项目旨在提高我们对健康和疾病中眼压调节的理解，并发现 治疗青光眼的更有效方法。

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.