Role of Capillary Flow and Autoregulation in Primary Open Angle Glaucoma

 描述（由申请人提供）：毛细血管血流和自身调节在原发性开角型青光眼中的作用项目总结该K23申请由Osamah Saeedi，MD提交，Osamah Saeedi是马里兰州，巴尔的摩大学眼科和视觉科学系的助理教授。我的长期目标是成为一名独立的临床研究者，专注于毛细血管水平的眼部血流在原发性开角型青光眼的发展和进展中的作用。为了实现这一目标，我提出了一个指导的职业发展计划，其中包括培训的新技术血管造影能够成像红细胞运动和定量的绝对血流量;人类受试者的培训;和临床试验的进行。在资助期间，我将获得临床研究硕士学位.原发性开角型青光眼（Primary open angle glaucoma，POAG）是世界范围内致盲的主要原因。虽然降低眼内压（IOP）仍然是唯一被证明有效的治疗方法，但许多患者仍然会出现不可逆的视力丧失，尽管有效的IOP降低治疗。因此，迫切需要鉴定POAG的替代的、潜在可改变的生物标志物。拟议的研究重点是识别和开发敏感的成像生物标志物，因为它们与毛细血管红细胞流动有关。有强有力的证据表明，血管成分在POAG的发展和进展。毛细血管红细胞流动（其不同于整体血流）是指毛细血管内的单个红细胞运动，其与血液循环的代谢能力密切相关以支持眼部组织。我的一位导师Robert Flower博士开发了先进的技术，使用红细胞介导的吲哚菁绿色血管造影术（EMA）和荧光介导的光电容积描记术（FM-PPG）在个体毛细血管水平上评估和量化眼部血流。EMA允许直接观察毛细血管内的红细胞运动，并定量红细胞速度和运动性以及局部红细胞压积。FM-PPG是一种允许使用吲哚菁绿色（ICG）血管造影术对血流进行绝对定量的方法。本研究的总体目标是确定毛细血管血流量和毛细血管红细胞流量在POAG中的作用。在具体目标1中，我建议进行横断面人体研究，以测量和比较POAG患者、POAG疑似患者和对照组的红细胞运动性、红细胞速度、血流量和局部红细胞压积。在具体目标2中，我建议进行横断面人体研究来测量这些变量的自动调节。我推测与对照组相比，POAG患者的红细胞速度和红细胞运动性较低，血流量较低，局部红细胞压积较低，血管自动调节较差。我进一步假设这些参数的局部变化与结构和功能性青光眼缺陷相关，特别是视网膜神经纤维层（RNFL）厚度和视野缺陷。

 DESCRIPTION (provided by applicant): The Role of Capillary Flow and Autoregulation in Primary Open Angle Glaucoma Project Summary This K23 application is submitted by Osamah Saeedi, MD, an Assistant Professor in the Department of Ophthalmology and Visual Sciences in the University of Maryland, Baltimore. My long-term goal is to become an independent clinical investigator focusing on the role of ocular blood flow at the capillary level in the development and progression of primary open angle glaucoma. Towards this goal, I propose a mentored career development plan that includes training in novel techniques of angiography capable of imaging erythrocyte movement and quantification of absolute blood flow; human subjects training; and the conduction of clinical trials. During the grant period I will obtain a Master's o Science in Clinical Research. Primary open angle glaucoma (POAG) is a leading cause of blindness worldwide. Although intraocular pressure (IOP) lowering remains the only proven therapy for the disease, many patients continue to experience irreversible vision loss despite effective IOP-lowering therapy. A critical need, therefore, exists to identify alternative, potentilly modifiable biomarkers for POAG. The proposed research focuses on identifying and developing sensitive imaging biomarkers as they relate to capillary erythrocyte flow. There is strong evidence for a vascular component in the development and progression of POAG. Capillary erythrocyte flow (which differs from bulk blood flow) refers to individual erythrocyte movement within the capillaries, which is closely linked to the metabolic capacity of blood circulations to support the ocular tissues. One of my mentors, Dr. Robert Flower, has developed advanced techniques to evaluate and quantify ocular blood flow at the individual capillary level, using Erythrocyte Mediated Indocyanine Green Angiography (EMA) and Fluorescent Mediated Photo-Photoplethysmography (FM-PPG). EMA permits direct observation of erythrocyte movement within the capillaries and quantification of erythrocyte velocity and motility as well as local hematocrit. FM-PPG is a method that allows for the absolute quantification of blood flow using Indocyanine Green (ICG) angiography. The overall goal of this research is to determine the role of capillary blood flow and capillary erythrocyte flow in POAG. In specific aim 1, I propose cross-sectional human studies to measure and compare erythrocyte motility, erythrocyte velocity, blood flow, and local hematocrit in patients with POAG, POAG suspects, and controls. In specific aim 2, I propose cross-sectional human studies to measure the autoregulation of these variables. I hypothesize that patients with POAG have less erythrocyte velocity and erythrocyte motility, lower blood flow, lower local hematocrit, and poorer vascular autoregulation as compared to controls. I further hypothesize that local changes in these parameters will correlate to structural and functional glaucomatous deficits, specifically retinal nerve fiber laye (RNFL) thickness and visual field deficits.