Contractile Modulation of Distal Aqueous Humor Drainage

远端房水引流的收缩调节

• 批准号: 10047725
• 负责人: CHEE HIAN TAN
• 金额: $ 9.99万
• 依托单位: SIGHTGENE, INC.
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-12-01 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10047725
• 关键词: Actins; Actomyosin; Address; Affect; Animals; Aqueous Humor; Back; Behavior; Biology; Blindness; Blood; Blood Vessels; Bypass; Caliber; California; Cells; Cellular biology; Characteristics; Ciliary Muscle; Clinical; Collagen; Contracts; Development; Dimensions; Disease; Distal; Drainage procedure; Endothelium; Epitopes; Eye; F-Actin; Glaucoma; Goals; Health; Health Benefit; Human; Knowledge; Label; Laboratories; Lead; Learning; Liquid substance; Lymphatic; Lymphatic System; Membrane; Modeling; Molecular; Molecular Biology; Mus; Mutant Strains Mice; Operative Surgical Procedures; PECAM1 gene; Pathogenesis; Pathway interactions; Patients; Perfusion; Pharmacology; Physiologic Intraocular Pressure; Physiology; Play; Regulation; Reporter; Research; Resistance; Risk Factors; Role; Sclera; Signal Transduction; Smooth Muscle; Smooth Muscle Actin Staining Method; Structure; Structure of sinus venosus of sclera; System; Therapeutic; Tissues; Trabecular meshwork structure; Tracer; Transgenic Mice; Transgenic Organisms; United States National Institutes of Health; Universities; Veins; Venous Pressure level; Vision; Work; aqueous; base; cadherin 5; caldesmon; calponin; cell growth regulation; cellular imaging; fluorophore; improved; in vivo; in vivo imaging; innovation; insight; limbal; lymphatic vessel; molecular imaging; molecular marker; novel; optogenetics; preservation; second harmonic generation imaging; tool; two photon microscopy

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.

项目摘要/摘要 研究远端水排水道及其调节的意义在于该道有助于 显着具有水性流出阻力。这种流出阻力是眼内压的主要决定因素 （IOP）。 IOP是青光眼的关键危险因素，青光眼是全球不可逆失明的主要原因。我们没有 了解如何调节IOP。通过什么意味着IOP在青光眼中的失调是 大多也是未知的。该项目的长期目标是提高我们对IOP监管的理解， 青光眼发病机理并发展更有效的临床疗法。这种改善的治疗应该更好 靶向IOP升高的潜在机制，以改变青光眼的自然疗程的方式 否则会导致失明。健康的好处将在更好地保存视力方面看到 影响患者的生活。 背景和科学需求。手术绕过小梁网的手术越来越多地执行 IOP并治疗青光眼。一旦高电阻网络组织，IOP就不会像预期的那样降低 但是，被绕过。然后必须在远端水排水道中保留对流出的显着阻力 位于小梁网和下游血管之间。因此，重要的是要了解 远端水流区的细胞组织及其对流出阻力的影响，但我们非常知道 关于它的工作原理几乎没有。这代表了我们科学知识中的一个重要差距，这是更好的障碍 了解和治疗青光眼。 创新。我们假设远端水排水道的墙有能力合同改变 道的口径和尺寸。这提供了调节水性流出阻力和IOP的机制。 我们试图确定远端收缩力的分子标记，并确定它们在调节中的作用 水幽默流出。 我们将通过2光子显微镜研究各种突变小鼠，该显微镜可以解决组织内的细胞以解决该细胞 具体目的是：（1）确定远端水排水道的细胞特征； （2）确定程度 存在收缩机制，并通过此途径影响流出。 影响。该项目旨在提高我们对健康和疾病中IOP调节的理解，并发现 治疗青光眼的更有效方法。