MECHANISMS OF RECURRENCE OF ANTERIOR UVEITIS OF THE EYE

眼睛前葡萄膜炎的复发机制

• 批准号: 2159101
• 负责人: Thomas Frank Freddo
• 金额: $ 29.64万
• 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 1996-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2159101
• 关键词: Aotus; Macaca fascicularis; actins; antiinflammatory agents; blood aqueous barrier; cell adhesion molecules; confocal scanning microscopy; digitonin; electron microscopy; eye; fluorescent dye /probe; fluorimetry; freeze etching; gap junctions; immune complex; inflammation; iridocyclitis; mathematical model; membrane permeability; model design /development; prednisolone; protein transport; relapse /recurrence; sterols; tight junctions

Idiopathic anterior uveitis in man is characterized by a breakdown of the blood-aqueous barrier (BAB) that is acute and often recurrent. Left untreated, it can lead to secondary glaucoma, or other complications. Currently available objective measures of severity provide little information regarding the dynamics of the inflammatory processes, especially the process of BAB repair during resolution. Knowledge of these process depends upon a thorough understanding of protein diffusional mechanics in the normal and inflamed eye. Our goal in these animals studies is to refine and validate an accurate computational model for use in deriving more information for BAB permeability studies of inflamed eyes using the non-invasive objective method of aqueous fluorophotometry (AF). Using fluoresceinated horseradish peroxidase, an intravascular tracer first introduced by our group, we have successfully compared results of in vivo AF studies with results of microscopic Tracer Localization studies, both perform on the same eyes, With this combined AFL method, it is possible to distinguish sites which have, from those which have not contributed to aqueous fluorescence in the inflamed eye, as measured by AF; a valuable tool with which corroborate certain predictions of computational models. Using our AFL method, we will examine the process of re-establishment of the BAB 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 zonulae adhaerentes and zonulae occludentes (tight junctions), which constitute the anatomic equivalents of the BAB. All of the procedures outlined above can be performed in conjunction with freeze- fracture, election microscopy and confocal,laser scanning microscopy to examine the roles of certain proteins involved in junctional re-assembly, such as F-actin, E-9 and ZO-1. Incomplete or faulty restoration of BAB permeability, after clinical evidence of an acute anterior uveitis has subsided, could provide repositories for immune-complex deposition, possibly contributing to recurrent anterior uveitis. We will also examine the re-appearance of gap junctions which are destroy by inflammation in the ciliary epithelium. A contributing role for these junctions in recovery from inflammation-induced ocular hypotension will be sought.

男性特发性前葡萄膜炎的特征是 血-房水屏障（BAB）是急性的，经常复发。 左 如果不及时治疗，会导致继发性青光眼或其他并发症。 目前可用的严重程度客观衡量标准提供的信息很少 关于炎症过程动力学的信息， 尤其是在消退过程中的BAB修复过程。 了解这些 这一过程取决于对蛋白质扩散的透彻理解。 在正常和发炎的眼睛力学。 我们在这些动物研究中的目标是完善和验证一个准确的 用于推导BAB更多信息的计算模型 使用非侵入性物镜对发炎眼睛的渗透性研究 水荧光光度法（AF）。 使用荧光辣根 过氧化物酶，血管内示踪剂首先介绍了我们的小组，我们有 成功比较了体内AF研究结果与 显微镜示踪剂定位研究，都在同一只眼睛上进行， 使用这种组合AFL方法，可以区分 有，从那些没有贡献的水荧光在 眼睛发炎，通过AF测量;一个有价值的工具， 计算模型的某些预测。 使用我们的AFL方法，我们将检查重建的过程， 前葡萄膜炎消退期间的BAB，包括伴和不伴 使用甾体和非甾体抗炎药治疗。 将特别强调与《公约》有关的机制， 粘连小带和闭合小带的重新组装（紧密 连接），其构成BAB的解剖学等同物。 所有 上述程序可以与冻结一起执行， 骨折，电子显微镜和共聚焦，激光扫描显微镜， 检查某些蛋白质在连接重组中的作用， 如F-肌动蛋白、E-9和ZO-1。 BAB修复不完整或错误 渗透性，在急性前葡萄膜炎的临床证据已经 沉降，可以提供免疫复合物沉积的储存库， 可能导致复发性前葡萄膜炎 我们亦会研究 间隙连接的重新出现，这些间隙连接被炎症破坏， 睫状上皮 这些连接在恢复中的贡献作用 将寻求炎症引起的低眼压。