In Vivo Characterizations of Retinal Hemodynamics

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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.