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 视网膜毛细血管内的微循环在支持高强度的代谢活动中起着关键作用。 内层视网膜和维持人眼的正常视网膜功能。氧气的输送和排出 组织水平的代谢废物很大程度上是由压缩和流动成单列的红细胞完成的 通过视网膜毛细血管。在单个毛细血管内，红细胞被周期性地加速 血流动力和流动阻力的阻碍。同时，毛细血管承受压力(剪切和 周向的)由血液流动引起的。对毛细血管中血流动力的生物反应- 血液复合体在血流控制和血管结构重塑中起着重要作用。在脉动的同时 红细胞在血管中的运动是氧气转移所必需的，也是毛细血管功能的关键 组织健康、过高的压力和血流脉动会损害毛细血管并导致靶器官损害。 眼球、全身和中枢神经系统(CNS)都有正常搏动功能障碍。 病理学。因此，人视网膜红细胞搏动性运动的活体特征 毛细血管对于了解视网膜、全身和中枢神经系统的病理生理学和促进 开发新的治疗方法。我们研制了一种新型的自适应光学近共焦检眼镜 (AONCO)能够精确测量心脏周期内的红细胞搏动速度 人类最细小的视网膜毛细血管。这种能力允许评估与以下有关的高阶动力学 反映随时间变化的血流动力的红细胞的加速，并通知机械 Strass被毛细管系统所忍受。我们假设高阶血流动力学特性是 视网膜毛细血管功能的基本指标，可作为检测微小或早期的敏感生物标志物 毛细血管病理生理学改变。因此，我们建议研究高阶动力学。 正常人黄斑单个毛细血管水平的红细胞流动 对于患有高血压和糖尿病的患者，使用AONCO。我们的目标有两个- Fold：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 用于检测与年龄和疾病相关的视网膜微循环变化的生物标志物。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/民族对健康受试者的影响。然后，我们将评估 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。 发展中的视网膜病变。我们的研究探索了一种评估视网膜毛细血管功能的新方法。这个 结果将对与全身CAN CNS情况相关的广泛领域产生很大影响。它可能会促进 通过提供对治疗效果的准确评估，开发新的治疗策略。