In Vivo Characterizations of Retinal Hemodynamics

项目摘要 视网膜毛细血管中的微循环在支持视网膜微血管的强烈代谢活动中起着关键作用。 内层视网膜并维持人眼正常的视网膜功能。输送氧气和清除 在组织水平上的代谢废物主要是由压缩并单列流动的红细胞完成的 通过视网膜毛细血管在单个毛细血管内，红细胞周期性地被 血流动力学力和流动阻力阻碍。同时，毛细血管承受应力（剪切和 周向的）。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建中起重要作用。虽然搏动 红细胞在血管中的运动对于氧传递是必需的，并且对于毛细血管功能是关键的 和组织健康，过度的压力和流动脉动会损害毛细血管并导致靶器官损伤 正常搏动性的破坏已经牵涉到眼部、全身和中枢神经系统（CNS） 病理学因此，在人视网膜中红细胞的脉动运动的体内表征是不确定的。 毛细血管对于理解视网膜、全身和CNS病理生理学和促进视网膜的 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），其能够精确测量心脏中的心动周期内的脉动红细胞速度。 最细的视网膜毛细血管这种能力允许评估与所述系统相关的高阶动力学。 红细胞的加速度反映了随时间变化的血液动力学力，并通知机械 毛细血管系统承受的压力。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，并且可以是用于检测小或早期视网膜病变的敏感生物标志物。 毛细血管病理生理学变化。因此，我们建议调查的高阶动力学的 红细胞在正常生理状态下的活体受试者的黄斑中以单毛细血管水平流动 和眼睛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液动力学，并开发新的 用于检测视网膜微循环中年龄和疾病相关变化的生物标志物。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 健康人类受试者中性别、年龄和种族/民族的影响。然后，我们将评估 高血压最后，我们将研究视网膜毛细血管血流动力学在糖尿病患者的风险增加， 发展成视网膜病我们的研究探讨了一种新的方法来评估视网膜毛细血管功能。的 结果将对与全身性CNS疾病相关的广泛领域产生重大影响。它可以促进 通过提供治疗效果的精确评估开发新的治疗策略。

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.