TY - JOUR
T1 - Enhanced inflow and outflow rates despite lower IOP in bestrophin-2- deficient mice
AU - Zhang, Youwen
AU - Davidson, Bryan R.
AU - Stamer, W. Daniel
AU - Barton, Jennifer K.
AU - Marmorstein, Lihua Y.
AU - Marmorstein, Alan D.
PY - 2009/2
Y1 - 2009/2
N2 - 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 (Ct), aqueous humor production (Fa), and anterior chamber volume (V a) were made using anterior chamber cannulation. Conventional (F c) and uveoscleral outflow (Fu), 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, Fa in Best2-/- mice was increased by ∼73% compared with Best2+/+ mice. This was accompanied by increases in Fc and Fu. 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 Fc and Fu, 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.
AB - 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 (Ct), aqueous humor production (Fa), and anterior chamber volume (V a) were made using anterior chamber cannulation. Conventional (F c) and uveoscleral outflow (Fu), 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, Fa in Best2-/- mice was increased by ∼73% compared with Best2+/+ mice. This was accompanied by increases in Fc and Fu. 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 Fc and Fu, 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.
UR - http://www.scopus.com/inward/record.url?scp=59449104663&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=59449104663&partnerID=8YFLogxK
U2 - 10.1167/iovs.08-2501
DO - 10.1167/iovs.08-2501
M3 - Article
C2 - 18936135
AN - SCOPUS:59449104663
SN - 0146-0404
VL - 50
SP - 765
EP - 770
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
IS - 2
ER -