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Publication : Enhanced inflow and outflow rates despite lower IOP in bestrophin-2-deficient mice.

First Author  Zhang Y Year  2009
Journal  Invest Ophthalmol Vis Sci Volume  50
Issue  2 Pages  765-70
PubMed ID  18936135 Mgi Jnum  J:146687
Mgi Id  MGI:3838253 Doi  10.1167/iovs.08-2501
Citation  Zhang Y, et al. (2009) Enhanced inflow and outflow rates despite lower IOP in bestrophin-2-deficient mice. Invest Ophthalmol Vis Sci 50(2):765-70
abstractText  PURPOSE: Bestrophin-2 (Best2), a putative Cl(-) channel is expressed in the nonpigmented epithelium (NPE). Disruption of Best2 in mice results in a diminished intraocular pressure (IOP). Aqueous humor dynamics were compared in Best2(+/+) and Best2(-/-) mice, to better understand the contribution of Best2 to IOP. METHODS: Measurements of IOP, episcleral venous pressure (EVP), conventional outflow facility (C(t)), aqueous humor production (F(a)), and anterior chamber volume (V(a)) were made using anterior chamber cannulation. Conventional (F(c)) and uveoscleral outflow (F(u)), and rate of aqueous humor turnover, were calculated from measured data. The anterior chamber was examined in live mice by optical coherence tomography (OCT) and postmortem by light microscopy. RESULTS: IOP in Best2(-/-) mice was lower compared with Best2(+/+) littermates. EVP was unchanged. Since Best2 is expressed in NPE cells, the hypothesis was that Best2 is involved in generating aqueous flow. However, F(a) in Best2(-/-) mice was increased by approximately 73% compared with Best2(+/+) mice. This was accompanied by increases in F(c) and F(u). Aqueous humor turnover was enhanced more than twofold in Best2(-/-) mice. No evidence of developmental structural changes was noted. CONCLUSIONS: Best2 appears to antagonize the formation of aqueous humor and cause an inhibition of both F(c) and F(u), despite being expressed only in NPE cells. These data support the hypothesis that the inflow and outflow pathways communicate via soluble agents present in the aqueous humor and implicate Best2 as a critical mediator of that communication.
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