Redefining the Model of the Blood-Aqueous Barrier

点击翻译按钮获取中文摘要

DESCRIPTION (provided by applicant): In the existing model of the blood-aqueous barrier (BAB), elevations in the very low levels of protein in the aqueous humor are attributed to increased permeability of the tight junctions in the iris vasculature and ciliary epithelium. But, based upon recent work by our group and others, there is reason to now challenge the validity of the present model. Using our revised model of the BAB, we hypothesize that certain previously reported clinical circumstances, in which protein levels rise or fall in aqueous humor, can be accounted for via physiological rather than pathological mechanisms. In the proposed studies, we will exploit each of these circumstances to challenge the vigor of our new model of the BAB. If our new model proves robust, it would change fundamental assumptions about the biological environment surrounding the crystalline lens and within the trabecular meshwork. These changes have potential implications in the pathobiology of cataract and glaucoma. The particular events to be examined include changes in aqueous protein levels associated with: 1) the use of medications that suppress aqueous humor formation, and 2) the use of miotics and mydriatics, Previous studies suffered from an inability to DIRECTLY assess kinetics in the posterior chamber of the eye and thus attributed changes in aqueous protein levels in each instance to altered permeability of the BAB's tight junctions. Using our high-resolution, contrast magnetic resonance imaging methods, the posterior chamber can be readily identified and changes in the amount and time-course of contrast material entering from the bloodstream can be detected and quantified. Most importantly, because these methods are non-invasive, nearly all of the proposed studies can be done directly in human volunteers. Preliminary studies in human volunteers suggest that the kinetics of the normal BAB in the new paradigm may differ between men and women. Thus, we will attempt to confirm and explain this observation and also look for changes in kinetics with age. We will use computational modeling of barrier kinetics to corroborate our experimental observations.