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B. K. Armstrong, R. M. Sappington-Calkins, D. J. Calkins, P. K. Russ, M. S. Chang; Antibodies Specific to the Extracellular Domain of Bves Lowers IOP. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4057.
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Blood Vessel Epicardial Substance (Bves) is novel adhesion molecule that regulates tight junction (TJ) formation. Presence of endogenous Bves has been detected in multiple adult ocular tissues including the trabecular meshwork. Since Bves regulates TJ formation and TJs have been implicated in aqueous outflow resistance, we hypothesize that disruption of Bves function in the anterior chamber (AC) will alter intra-ocular pressure (IOP).
To test our hypothesis, polyclonal antibodies (Ab) targeting extracellular (EC) and intracellular (IC) domains of Bves were intracamerally injected in Brown Norway rats with normal or elevated IOP achieved by microinjection of 5 ul of polystyrene microbreads. In normal IOP animals, one eye received EC-Ab and the fellow eye received IC-Ab at the same volume and concentration. Antibody treatments were also compared to same volume normal saline injections. In the elevated IOP model, animals received injections of Bves antibodies with the microbeads. The fellow eye served as control and received same volume injection of microbeads alone. Conscious Tono-pen measurements were carried out daily after injection for 10 days. Immunofluorescent staining of the anterior segment was carried at various time points to examine the spatial and temporal distribution of Bves antibodies in the anterior chamber.
: Intracameral injections of Ab targeting of the EC-Ab significantly lowered IOP by 4-5 mm Hg for 4 days in rats with normal IOP. There is no decrease in IOP with IC-Ab or saline injections. Microbead injections elevated IOP +10-15 mm Hg for 3-4 weeks, while injections of microbeads plus EC antibodies resulted in a negative cumulative pressure effect up to 5 days after injection. Injections of microbead plus IC-Ab exhibited similar IOP elevations with similar increasing cumulative pressure effects. Immunohistochemistry confirms the localization of the EC-Bves antibodies to the region of the trabecular meshwork.
Our findings indicate that antibodies targeting the extracellular domain of Bves lower IOP in animal models with both normal and elevated IOP. A potential mechanism for IOP lowering effect is disruption of TJs in trabecular meshwork and Schlemm’s Canal, since Bves is needed for the maintenance of TJs. These findings may provide insight into novel regulatory pathways of aqueous outflow and lead to new treatment for glaucoma.
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