In Vivo Characterizations of Retinal Hemodynamics

视网膜血流动力学的体内表征

• 批准号: 10503497
• 负责人: Yuhua Liang Zhang
• 金额: $ 39.36万
• 依托单位: DOHENY EYE INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-30 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10503497
• 关键词: Acceleration; Affect; Age; Angiography; Animals; Antihypertensive Agents; Area; Background Diabetic Retinopathy; Biological; Biological Markers; Biological Models; Blindness; Blood; Blood Circulation; Blood Pressure; Blood Vessels; Blood capillaries; Blood flow; Cardiac; Cardiovascular system; Characteristics; Circadian Rhythms; Clinical; Complex; Development; Diabetes Mellitus; Diabetic Retinopathy; Disease; Disease Progression; Erythrocytes; Essential Hypertension; Ethnic Origin; Evaluation; Event; Excision; Eye; Functional disorder; Gender; Goals; Health; Human; Hypertension; Individual; Intervention; Knowledge; Measurement; Measures; Mechanics; Metabolic; Methods; Microcirculation; Microvascular Dysfunction; Movement; Neuraxis; Ophthalmoscopes; Ophthalmoscopy; Optical Coherence Tomography; Organ; Outcome; Oxygen; Pathology; Patients; Pharmaceutical Preparations; Physiologic pulse; Physiological Processes; Play; Pulsatile Flow; Race; Resistance; Retina; Retinal Diseases; Risk; Role; Site; Speed; Stress; System; Systemic disease; Therapeutic Intervention; Time; Tissues; Treatment Efficacy; Variant; Vision; adaptive optics; arterial stiffness; base; cardiovascular risk factor; clinically significant; diabetic patient; disorder risk; electric impedance; hemodynamics; human subject; hypertensive; improved; in vivo; macula; novel; patient population; pressure; prevent; response; spatial temporal variation; trait; treatment strategy; wasting

Project Abstract Microcirculation in retinal capillaries plays a critical role in support of the intense metabolic activities of the inner retina and for maintaining normal retinal function in the human eye. The delivery oxygen and removal of metabolic waste at the tissue level is largely accomplished by erythrocytes that compress and flow in single file through retinal capillaries. Within single capillaries, the erythrocytes are accelerated periodically by the hemodynamic force and impeded by flow resistance. Meanwhile, the capillaries endure stress (shear and circumferential) resulting from the blood flow. Biological responses to the hemodynamic forces in the capillary- blood complex play an important role in blood flow control and vessel structural remodeling. While pulsatile movement of erythrocytes in the blood vessel is essential for oxygen transfer and critical for capillary function and tissue health, excess pressure and flow pulsatility can harm capillaries and result in target organ damage Disruption of normal pulsatility has been implicated in ocular, systemic and central nervous system (CNS) pathologies. Thus, in vivo characterization of the pulsatile movement of the erythrocytes in human retinal capillaries is significant for understanding retinal, systemic and CNS pathophysiology and facilitating the development of novel treatments. We have developed a novel adaptive optics near-confocal ophthalmoscope (AONCO) which enables precise measurement of the pulsatile erythrocyte velocity within a cardiac cycle in the finest human retinal capillaries. This ability allows for evaluating high order dynamics pertaining to the acceleration of the erythrocytes that reflects the time varying hemodynamic forces, and informs the mechanical strass endured by the capillary system. We hypothesize that high-order hemodynamic characteristics are fundamental measures of retinal capillary function and can be sensitive biomarkers for detecting small or early changes in capillary pathophysiology. We thus propose to investigate the high-order dynamics of the erythrocyte flow at the single capillary level in the maculae of living human subjects who are in normal physical and ocular health and in patients with hypertension and diabetes, using the AONCO. Our objectives are two- fold: better understanding high order hemodynamics in human retinal capillaries and developing new biomarkers for detecting age- and disease-related changes in retinal microcirculation. To achieve these goals, first, we will investigate the spatial and temporal variation of high order hemodynamics and characterize the influence of gender, age, and race/ethnicity in healthy human subjects. Then, we will evaluate the impact of hypertension. Finally, we will examine retinal capillary hemodynamics in diabetic patients at increasing risk for developing retinopathy. Our study investigates a novel method for assessing retinal capillary function. The outcome will have high impact on broad field relating to systemic can CNS conditions. It may facilitate the development of novel treatment strategies by providing precise assessment of the therapeutic efficacy.

项目摘要 视网膜毛细血管的微循环在支持视网膜的强烈代谢活动中起着至关重要的作用 视网膜内部并维持人眼的正常视网膜功能。输送氧气和去除 组织水平的代谢废物主要是由红细胞完成的，红细胞在单列中压缩和流动 通过视网膜毛细血管。在单个毛细血管内，红细胞周期性地加速 血流动力并受到流动阻力的阻碍。同时，毛细血管承受压力（剪切力和 圆周）由血流产生。对毛细血管中血流动力学的生物反应 血液复合物在血流控制和血管结构重塑中发挥重要作用。当有搏动时 血管中红细胞的运动对于氧气输送至关重要，对毛细血管功能也至关重要 和组织健康、超压和血流脉动会损害毛细血管并导致靶器官损伤 正常搏动的破坏与眼部、全身和中枢神经系统 (CNS) 有关 病理学。因此，人视网膜中红细胞脉动运动的体内表征 毛细血管对于理解视网膜、全身和中枢神经系统病理生理学并促进 开发新的治疗方法。我们开发了一种新型自适应光学近共焦检眼镜 （AONCO）能够精确测量心动周期内的脉动红细胞速度 最细的人类视网膜毛细血管。这种能力允许评估与 红细胞的加速度反映了随时间变化的血流动力学力，并通知机械 毛细管系统承受的压力。我们假设高阶血流动力学特征是 视网膜毛细血管功能的基本测量，可以作为检测小或早期的敏感生物标志物 毛细血管病理生理学的变化。因此，我们建议研究的高阶动力学 处于正常身体状况的活人受试者黄斑中单个毛细血管水平的红细胞流量 和眼部健康以及高血压和糖尿病患者，使用 AONCO。我们的目标有两个—— 折叠：更好地了解人类视网膜毛细血管的高阶血流动力学并开发新的 用于检测视网膜微循环中与年龄和疾病相关的变化的生物标志物。为了实现这些目标， 首先，我们将研究高阶血流动力学的空间和时间变化并表征 性别、年龄和种族/民族对健康人类受试者的影响。然后，我们将评估影响 高血压。最后，我们将检查糖尿病患者的视网膜毛细血管血流动力学，其风险增加 发展为视网膜病变。我们的研究探讨了一种评估视网膜毛细血管功能的新方法。这 结果将对与系统性中枢神经系统疾病相关的广泛领域产生重大影响。它可能会促进 通过提供精确的治疗效果评估来开发新的治疗策略。