MECHANISMS OF RECURRENCE OF ANTERIOR UVEITIS OF THE EYE

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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.