Noninvasive Imaging of Chorioretinal Oxygen Tension

描述（由申请人提供）：视网膜内细胞的代谢功能依赖于视网膜循环提供的营养和氧气的可用性。视网膜内缺氧与常见的致盲性人眼疾病有关，如糖尿病视网膜病变和视网膜血管闭塞。然而，氧在血管病变发展中的作用仍未完全了解。为了全面评估视网膜内部组织的活力，需要了解血管和组织的氧含量、血流量和氧的代谢率。此外，视网膜氧合制图对于全面识别局部病理异常是必要的。迄今为止进行的研究并没有一起测量这些参数或超过扩展的视网膜区域。因此，对视网膜缺血引起的血管灌注不良、组织缺氧和能量代谢障碍之间的相互作用了解有限。本研究计划的目的是提供一个全面的研究在正常和挑战生理条件下的视网膜内氧动力学，以及实验缺血状态。这项研究将有可能使用我们的新视网膜血管和组织氧张力（PO2）测绘技术加上血流量测量。具体目的是：1)确定实验性糖尿病患者视网膜血管PO2、微血管PO2梯度和视网膜内氧提取分数的异常情况；2)开发一种新型成像系统，用于同时测量视网膜血管PO2和血流，并得出视网膜内氧代谢率（MO2）的测量值；3)确定视网膜血流、视网膜内MO2和组织PO2对光闪烁视觉刺激的正常反应

DESCRIPTION (provided by applicant): The metabolic function of cells in the inner retina relies on the availability of nutrients and oxygen that are supplied by the retinal circulation. Iner retinal hypoxia is implicated in common and blinding human eye diseases, such as diabetic retinopathy and retinal vascular occlusions. However, the role of oxygen in the development of vascular pathologies is still not completely understood. For a complete assessment of inner retinal tissue vitality, knowledge of vascular and tissue oxygen content, blood flow, and metabolic rate of oxygen is required. Additionally, mapping of retinal oxygenation is necessary for identification of localized pathological abnormalities in a comprehensive manner. Studies performed thus far have not measured these parameters together or over extended retinal areas. Therefore, there is limited knowledge of the interplay among vascular malperfusion, tissue hypoxia, and energy metabolism impairment due to retinal ischemic conditions. The objective of the research proposal is to provide a comprehensive study of oxygen dynamics in the inner retina under normal and challenged physiological conditions, and experimental ischemic states. The study will be possible with the use of our novel retinal vascular and tissue oxygen tension (PO2) mapping technique coupled with blood flow measurements. The specific aims are to: 1) determine abnormalities in retinal vascular PO2, gradients of microvascular PO2, and inner retina oxygen extraction fraction in experimental diabetes, 2) develop a novel imaging system for simultaneous measurements of retinal vascular PO2 and blood flow, and derive measurements of inner retinal metabolic rate of oxygen (MO2), 3) determine normal responses of retinal blood flow, inner retinal MO2 and tissue PO2 to visual stimulation by light flicker, and 4) map the spatial distribution and degrees of retinal hypoxia in experimental diabetes and retinal arterial occlusion. The findings will impact the field by broadening knowledge of coupling between retinal blood flow and oxidative metabolism under a normal physiological condition and elucidate retinal oxygen dynamics in the pathogenesis of diabetic retinopathy and retinal vascular occlusions. PUBLIC HEALTH RELEVANCE: Retinal hypoxia is implicated in the development of major and common blinding human eye diseases, such as diabetic retinopathy. A better understanding of retinal oxygen dynamics is greatly needed to advance the available diagnostic and therapeutic procedures for retinal ischemic diseases. The proposed research will provide a complete study of retinal oxygen dynamics under normal, physiologically altered, and experimentally induced pathologic conditions. The findings of the study will enable future assessment of therapies for diabetic retinopathy (vitrectomy and laser treatment) and emerging therapeutic interventions (anti-VEGF and corticosteroids), to increase their effectiveness by more timely application.