In Vivo Imaging of Leukocyte-Endothelial Dynamics

描述（由申请方提供）：白细胞迁移穿过血管内皮屏障的过程是炎症过程和感染反应的基础。我们将定量各种药物如局部皮质类固醇、口服非甾体抗炎药和肥大细胞稳定剂在其中几个过程中的作用。我们已经在动物系统中应用活体显微镜来可视化，定量和分析这一过程。 最近在共聚焦显微镜的进展，使一个欧洲小组定量白细胞内皮滚动和粘附在微血管的人的眼睛。 结合我们在共聚焦显微镜和我们的经验分析白细胞血管相互作用的临床专业知识，我们建议利用在体内共聚焦技术来定量白细胞滚动和逮捕4个不同的人类血管床：利姆布斯，结膜，巩膜外层，巩膜。 有这三个具体的目标：目标一，我们提出的图像滚动和粘白细胞在四个不同的正常眼血管床：结膜，利姆布斯，巩膜外层，巩膜。 目的二，我们将比较七种疾病状态下特定血管床中的白细胞内皮动力学：a）过敏性季节性结膜炎，B）干燥综合征和干眼，c）睑缘炎，d）移植物抗宿主病（GVHD），e）巩膜外层炎，f）巩膜炎，和g）前葡萄膜炎。 目的三，我们将确定药物的效果，包括局部醋酸泼尼松龙，肥大细胞稳定剂（optipranolol），或口服非甾体抗炎药（吲哚美辛）对内皮细胞的动力学疾病，每一个经常开处方。 我们的研究将直接阐明几个棘手的和很少研究的眼病过程的发病机制。 这些研究将阐明药物改变这些过程的机制。 最重要的是，这些研究将量化以前没有成像的微血管床中的基本人类生物学过程。

DESCRIPTION (provided by applicant): The process of leukocyte migration across the vascular endothelial barrier is fundamental to the process of inflammation and the response to infection. We will quantitate the effect of various medications such as topical corticosteroids, oral nonsteroidal anti-inflammatory drugs, and mast cell stabilizers in several of these processes. We have applied intravital microscopy in animal systems to visualize, quantitate and analyze this process. Recent advances in confocal microscopy have allowed a European group to quantitate leukocyte endothelial rolling and sticking in the microvasculature of the human eye. Combining our clinical expertise in confocal microscopy and our experience analyzing leukocyte vascular interactions, we propose to utilize in vivo confocal technology to quantitate leukocyte rolling and arrest in 4 different human vascular beds: the limbus, conjuctiva, episclera, and sclera. With these three specific aims: Aim one, we propose to image rolling and sticking of leukocytes in four different normal ocular vascular beds: the conjunctiva, limbus, episclera, and sclera. Aim two, we will compare leukocyte-endothelial dynamics in specific vascular beds in seven disease states: a) allergic seasonal conjunctivitis, b) Sjogren's syndrome and dry eye, c) blepharitis, d) graft versus host disease (GVHD), e) episcleritis, f) scleritis, and g) anterior uveitis. Aim three, we will determine the effect of medications including topical prednisolone acetate, a mast cell stabilizer (optipranolol), or an oral nonsteroidal anti-inflammatory drug (indomethacin) on endothelial-leukocyte dynamics in diseases for which each is frequently prescribed. Our studies will directly clarify the pathogenesis of several troublesome and rarely studied ocular disease processes. These studies will elucidate the mechanism by which medications alter these processes. Most importantly these studies will quantitate a fundamental human biological process in microvascular beds that have not previously been imaged.