MECHANISMS OF RECURRENCE OF ANTERIOR UVEITIS OF THE EYE

眼睛前葡萄膜炎的复发机制

• 批准号: 3259018
• 负责人: Thomas Frank Freddo
• 金额: $ 20.7万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-01-01 至 1991-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3259018
• 关键词: Pongidae; antiinflammatory agents; blood aqueous barrier; electron microscopy; eye agent; eye disorder diagnosis; eye infections; freeze etching; gap junctions; glaucoma; intraocular pressure; laboratory rabbit; noninvasive diagnosis; relapse /recurrence; uveitis

Idiopathic anterior uveitis in man is characterized by a breakdown of the blood-aqueous barrier which is acute and often recurrent. Left untreated, it can frequently lead to secondary glaucoma. Currently available objective measures of ocular inflammation necessitate undesirable invasive procedures such as paracentesis. Thus, clinical assessment of the severity of anterior uveitis and its response to therapy, has relied heavily upon subjective grading of such parameters as flare and cells. A major aim of the proposed studies is adaptation of the technique of aqueous fluorophotometry to the objective, but non-invasive measure of anterior segment inflammation. Eventual direct, clinical application of the procedure is our ultimate goal. Aqueous fluorophotometry will be used to measure the changes in severity of a bacterial endotoxin-induced model of anterior uveitis in rabbits and later in monkeys. By taking advantage of a new method developed in our laboratory, we can compare fluorophotometric estimates of severity with results of ultrastructural tracer studies on the same eyes. The ability to distinguish between sites which do and do not contribute to aqueous fluorescence at each stage of uveitis severity provides a valuable tool with which to refine pharmacokinetic models necessary to interpret fluorophotometric data in a clinical setting. Using the same procedures, in conjunction with the freeze-fracture technique, we will examine the process of re-establishment of the blood-aqueous barrier during resolution of anterior uveitis, both with and without treatment using steroidal and non-steroidal anti-inflammatory agents. Particular emphasis will be given to the mechanisms involved in the reassembly of tight junctions, which constitute the anatomic equivalent of the blood-aqueous barrier. Incomplete or faulty barrier reformation, after uveitis, could contribute to recurrence. Thus knowledge of the process of barrier reformation may be critical to an understanding of recurrent anterior uveitis in man. Additional animal models of increased blood-aqueous barrier permeability without appreciable inflammatory cell responses will be exploited to better understand the relationship between flare and fluorophotometrically measured aqueous fluorescence. Finally, studies in rabbits will determine if changes in intraocular pressure caused by inflammation are paralleled by changes in the size or number of gap junctions in the ciliary epithelium of these eyes.

男性特发性前葡萄膜炎的特点是 血-房水屏障是一种急性且经常复发的疾病。听之任之， 它经常会导致继发性青光眼。目前可用 眼部炎症的客观测量需要不受欢迎的侵入性 如穿刺术之类的程序。因此，临床评估严重程度 前葡萄膜炎及其对治疗的反应严重依赖于 对耀斑和细胞等参数进行主观分级。的一个主要目标 建议的研究是对水溶液技术的改编 荧光分光光度法可客观、非侵入性地测量前部 节段性炎症。最终直接在临床上应用 程序是我们的最终目标。 将使用水荧光光度法来测量严重程度的变化 细菌内毒素诱导兔前葡萄膜炎模型的建立 后来在猴子身上。利用我们开发的一种新方法 实验室，我们可以将荧光光度法估计的严重程度与 同一只眼睛的超微结构示踪剂研究结果。有能力 区分哪些部位对水有贡献，哪些不对水有贡献 在葡萄膜炎严重程度的每个阶段的荧光提供了一个有价值的工具 用它来完善解释所需的药代动力学模型 临床环境中的荧光光度数据。使用相同的程序， 结合冷冻断裂技术，我们将检查 在分解过程中重建血-房水屏障的过程 使用和不使用类固醇和非激素治疗的前葡萄膜炎 非类固醇抗炎药。将特别强调 与重新组装紧密连接所涉及的机制有关，这 构成了血-房水屏障的解剖学等价物。 葡萄膜炎后不完全或有缺陷的屏障改革可能会起到作用。 为了复发。因此，对壁垒改革过程的了解可能是 对了解人类复发性前葡萄膜炎至关重要。 血-房水屏障通透性增加的其他动物模型 没有可察觉的炎性细胞反应将被利用来更好地 从光度学角度了解耀斑和荧光的关系 测量的水溶液荧光。 最后，对兔子的研究将确定眼球内的变化 炎症引起的压力与大小或 这些眼睛的睫状上皮中的缝隙连接的数量。