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

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.