MECHANISMS OF RECURRENCE OF ANTERIOR UVEITIS OF THE EYE

点击翻译按钮获取中文摘要

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.