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Y. Zhang, B. Bakall, P. McLaughlin, L. Y. Marmorstein, A. Marmorstein; Bestrophin-2 and Generation of Intraocular Pressure. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5862.
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Bestrophin-2 (Best2) is expressed in the non-pigmented epithelial (NPE) cells of the ciliary body. Nothing is known of its physiological function in the eye. The purpose of this study was to determine whether the absence of Best2 affects aqueous humor dynamics in Best2 knock-out mice.
We have previously reported on the generation of Best2-/- mice and the localization of Best2 gene and protein expression to NPE cells. IOP measurements were made by cannulation of the anterior chamber. Measurements were made in mice aged 2-4 months and performed between 2:00 PM and 6:00 PM to minimize diurnal pressure variations. In studies using brinzolamide (1.0% soln) or timolol (0.5% soln) the drug was applied topically 2 hrs prior to measurement of IOP.
Best2-/- mice were found to have significantly (p<0.02) diminished IOP, (10.56 ± 0.21 mm Hg, n=39) in comparison to Best2+/+ (11.73 ± 0.37 mm Hg, n=12) and Best2+/- littermates (11.52 ± 0.44 mm Hg, n=20). There was no difference in episcleral venous pressure between genotypes with all having an EVP of 6.3 ± 0.3 mm Hg. Timolol and brinzolamide lowered IOP significantly in mice of all genotypes. While Timolol was equally effective on all genotypes, bringing IOP to ~9.5 mm Hg, brinzolamide lowered IOP in Best2-/- and Best2+/- mice by 0.5 and 0.7 mmHg more than in Best2+/+ mice. Pilot studies examining the inflow and outflow pathways suggest that the absence of Best2 results in changes to both the rate of aqueous formation and drainage.
Based on these studies we conclude that Best2 plays a role in the generation of IOP by regulating formation of aqueous humor, and that the inhibition of Best2 function represents an attractive new avenue for regulating IOP in individuals with glaucoma.
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