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.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
Project #
Application #
Study Section
Visual Sciences A Study Section (VISA)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Boston University
Schools of Medicine
United States
Zip Code
Freddo, Thomas F (2013) A contemporary concept of the blood-aqueous barrier. Prog Retin Eye Res 32:181-95
Kolodny, N H; Goode, S T; Ryan, W et al. (2002) Evaluation of therapeutic effectiveness using MR imaging in a rabbit model of anterior uveitis. Exp Eye Res 74:483-91
Sonsino, Jeffrey; Gong, Haiyan; Wu, Ping et al. (2002) Co-localization of junction-associated proteins of the human blood--aqueous barrier: occludin, ZO-1 and F-actin. Exp Eye Res 74:123-9
Freddo, T F (2001) Shifting the paradigm of the blood-aqueous barrier. Exp Eye Res 73:581-92
Wu, P; Gong, H; Richman, R et al. (2000) Localization of occludin, ZO-1, and pan-cadherin in rabbit ciliary epithelium and iris vascular endothelium. Histochem Cell Biol 114:303-10
Krenzer, K L; Freddo, T F (1997) Cytokeratin expression in normal human bulbar conjunctiva obtained by impression cytology. Invest Ophthalmol Vis Sci 38:142-52
Gong, H; Johnson, M; Ye, W et al. (1997) The non-uniform distribution of albumin in human and bovine cornea. Exp Eye Res 65:747-56
Freddo, T F (1996) Ultrastructure of the iris. Microsc Res Tech 33:369-89
Kolodny, N H; Freddo, T F; Lawrence, B A et al. (1996) Contrast-enhanced magnetic resonance imaging confirmation of an anterior protein pathway in normal rabbit eyes. Invest Ophthalmol Vis Sci 37:1602-7
Johnson, M; Gong, H; Freddo, T F et al. (1993) Serum proteins and aqueous outflow resistance in bovine eyes. Invest Ophthalmol Vis Sci 34:3549-57

Showing the most recent 10 out of 23 publications