TY - JOUR
T1 - The bovine arterially-perfused Eye
T2 - An in vitro method for the study of drug mechanisms on IOP, aqueous humour formation and uveal vasculature
AU - Wilson, William S.
AU - Shahidullah, Mohammad
AU - Millar, Cameron
N1 - Funding Information:
ACKNOWLEDGEMENTS This work has been generously supported by the W. H. Ross Foundation for the Prevention of Blindness in Scotland. M.S. holds a scholarship from the Association of Commonwealth Universities.
PY - 1993
Y1 - 1993
N2 - A method is reported in which the isolated bovine eye is perfused through a long posterior ciliary artery with buffered physiological saline, to provide simultaneous monitoring of drug effects on intraocular pressure (IOP), vascular resistance and the condition of the blood-aqueous barrier. With perfusion under constant pressure of 45 mm Hg, perfusate flows at 1.64 ± 0.12 tnl.min-1 (mean ± SEM) and IOP is 7.26 ± 0.16 mm Hg. Applying a constant flow rate of 2.25 ml.min-1, IOP averages 10.19 ± 0.32 mm Hg and in both cases this can be maintained for around 2h. Increasing the perfusion flow rate from 1.5 to 3.5 ml.min-1 produces a 76% rise in perfusion pressure but IOP increases only insignificantly (<10% The inclusion in the perfusion fluid of dextran and albumin to maintain oncotic pressure similar to that of plasma makes no difference to the IOP achieved and does not affect the leakiness of the barrier. The preparation shows a net consumption of oxygen, supporting the hypothesis that the aqueous humour formed is secreted by active transport processes. Timolol (in bolus doses of 1-300 nmol) injected into the perfusing fluid is shown to induce a dose-dependent fall in IOP within 5 min, reaching a steady state within 40 min. Timolol, however, causes no significant change in vascular resistance, whether this is measured as perfusion flow rate under constant pressure or as perfusion pressure at constant flow rate, nor does it alter the permeability of the barrier. Other beta-blockers such as oxprenolol and betaxolol also induce dose-dependent decreases in IOP. By applying a fluorescein dilution technique, it is found that the aqueous formation rate (Kout = 0.0046 min-1, or 12.9 μ1.min-1) is also reduced by timolol and, in a dose-dependent manner, by the new carbonic anhydrase inhibitor, MK-927. The bovine perfused eye offers a useful method for studying the mechanisms of action of drugs on IOP and aqueous humour formation, in isolation from the complicating influences of the CNS and the cardiovascular system and without the necessity to kill animals for experimental purposes.
AB - A method is reported in which the isolated bovine eye is perfused through a long posterior ciliary artery with buffered physiological saline, to provide simultaneous monitoring of drug effects on intraocular pressure (IOP), vascular resistance and the condition of the blood-aqueous barrier. With perfusion under constant pressure of 45 mm Hg, perfusate flows at 1.64 ± 0.12 tnl.min-1 (mean ± SEM) and IOP is 7.26 ± 0.16 mm Hg. Applying a constant flow rate of 2.25 ml.min-1, IOP averages 10.19 ± 0.32 mm Hg and in both cases this can be maintained for around 2h. Increasing the perfusion flow rate from 1.5 to 3.5 ml.min-1 produces a 76% rise in perfusion pressure but IOP increases only insignificantly (<10% The inclusion in the perfusion fluid of dextran and albumin to maintain oncotic pressure similar to that of plasma makes no difference to the IOP achieved and does not affect the leakiness of the barrier. The preparation shows a net consumption of oxygen, supporting the hypothesis that the aqueous humour formed is secreted by active transport processes. Timolol (in bolus doses of 1-300 nmol) injected into the perfusing fluid is shown to induce a dose-dependent fall in IOP within 5 min, reaching a steady state within 40 min. Timolol, however, causes no significant change in vascular resistance, whether this is measured as perfusion flow rate under constant pressure or as perfusion pressure at constant flow rate, nor does it alter the permeability of the barrier. Other beta-blockers such as oxprenolol and betaxolol also induce dose-dependent decreases in IOP. By applying a fluorescein dilution technique, it is found that the aqueous formation rate (Kout = 0.0046 min-1, or 12.9 μ1.min-1) is also reduced by timolol and, in a dose-dependent manner, by the new carbonic anhydrase inhibitor, MK-927. The bovine perfused eye offers a useful method for studying the mechanisms of action of drugs on IOP and aqueous humour formation, in isolation from the complicating influences of the CNS and the cardiovascular system and without the necessity to kill animals for experimental purposes.
UR - http://www.scopus.com/inward/record.url?scp=0027248936&partnerID=8YFLogxK
U2 - 10.3109/02713689309001840
DO - 10.3109/02713689309001840
M3 - Article
C2 - 7693396
AN - SCOPUS:0027248936
SN - 0271-3683
VL - 12
SP - 609
EP - 620
JO - Current Eye Research
JF - Current Eye Research
IS - 7
ER -