Noninvasive Imaging of Chorioretinal Oxygen Tension

描述(申请人提供)：视网膜内细胞的新陈代谢功能依赖于由视网膜循环提供的营养和氧气的可用性。视网膜缺氧与糖尿病视网膜病变和视网膜血管闭塞等常见致盲的人类眼病有关。然而，氧在血管病理发展中的作用仍不完全清楚。对于视网膜内组织活力的完整评估，需要了解血管和组织的含氧量、血流量和氧的代谢率。此外，视网膜氧合图对于全面识别局部的病理异常是必要的。到目前为止，进行的研究还没有一起测量这些参数，或者在扩大的视网膜区域测量这些参数。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的了解有限。该研究计划的目的是提供在正常和挑战的生理条件下以及实验性缺血状态下视网膜内氧动力学的全面研究。通过使用我们新的视网膜血管和组织氧分压(PO2)映射技术以及血流测量，这项研究将成为可能。其具体目的是：1)确定实验性糖尿病视网膜血管PO2、微血管PO2梯度和视网膜内氧摄取分数的异常；2)开发一种新的同时测量视网膜血管PO2和血流量的成像系统，并推导出测量视网膜内氧代谢速率(MO2)的方法；3)确定视网膜血流量、视网膜内MO2和组织PO2对闪光视觉刺激的正常反应；以及 4)绘制实验性糖尿病和视网膜动脉阻塞视网膜缺氧的空间分布和程度图。这些发现将通过拓宽对正常生理条件下视网膜血流和氧化代谢之间耦合的认识来影响该领域，并阐明糖尿病视网膜病变和视网膜血管阻塞的发病机制中的视网膜氧动力学。 公共卫生相关性：视网膜缺氧与主要和常见的致盲人类疾病的发展有关，如糖尿病视网膜病变。为了推进视网膜缺血性疾病的诊断和治疗，更好地了解视网膜氧动力学是非常必要的。这项拟议的研究将提供在正常、生理改变和实验诱导的病理条件下视网膜氧动力学的完整研究。这项研究的结果将使未来能够评估糖尿病视网膜病变的治疗方法(玻璃体切除和激光治疗)和新兴的治疗干预措施(抗血管内皮生长因子和皮质类固醇)，以通过更及时的应用来提高它们的有效性。

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.