Effects of endothelin-1 on intraocular pressure and aqueous humor dynamics in the rabbit eye

Abstract

The effects of endothelin-1 (ET-1) on intraocular pressure (IOP) and aqueous humor dynamics were studied in the rabbit eye. The intravitreal injection of 10(-5) M ET-1 (20 microliters) produced a biphasic IOP response consisting of an initial rise of 1 to 2 hours in duration, and a subsequent prolonged reduction lasting for more than 96 hours. Aqueous humor dynamics were determined 24 hours after the 10(-5) M ET-1 injection. Aqueous humor formation, measured fluorophotometrically, was decreased by 58%. Total outflow facility increased by 94%, according to measurement by two-level constant pressure perfusion. The change of uveoscleral outflow determined by fluorescein-dextran perfusion was not significant. The decrease in aqueous flow and the increase in total facility accounted for most of the IOP reduction after the ET-1 injection. Endothelin, which is endogenously present in the eye, may play a role in the regulation of intraocular pressure.

Endothelin‐1 effects on aqueous humor dynamics in monkeys

“…The suppression of aqueous humor flow previously reported in rabbits (Taniguchi et al 1994) also was not observed in our monkeys. These negative results are reported here.…”

“…There was a small but significant bilateral increase at the 1 mM dose (treated/BLΩ1.19∫0.05, p∞0.01; control/ BLΩ1.27∫0.10, p∞0.05) but no difference between the eyes (Trt/ContΩ 1.00∫0.09; Trt/BL vs Cont/BLΩ 0.95∫0.05). An increase in AHF would not be expected based on the aqueous flow reduction reported in rabbits (Taniguchi et al 1994). …”

“…Twelve hr prior to the first fluorophotometry scan monkeys received 20 ml of 10 mM (nΩ8, final concentrationΩ0.1 mM) or 100 mM (nΩ7, final concentrationΩ1.0 mM, 2 monkeys the same as in the first group) ET-1 in 0.01% aqueous acetic acid intravitreally in one eye (Kaufman et al 1981;Kee et al 1994), vehicle in the other. The time point chosen to begin fluorophotometry scans was based on the reported ∂40% (2.5 mg dose) (MacCumber et al 1991) or 10-12% (0.5 mg dose) (Taniguchi et al 1994) IOP reduction in rabbits 12 hr after intravitreal injection of ET-1. Aqueous acetic acid (10ml glacial acetic acid in 100 ml water) was used as the diluent as described by Taniguchi (Taniguchi et al 1994) A 30 G needle, connected to PE60 polyethylene tubing and a microsyringe, was inserted transconjunctivally perpendicular to the globe through the pars plana 4 mm posterior to the limbus, to a depth of 4mm at the 10 (OD) or 2 o'clock (OS) position.…”

“…The time point chosen to begin fluorophotometry scans was based on the reported ∂40% (2.5 mg dose) (MacCumber et al 1991) or 10-12% (0.5 mg dose) (Taniguchi et al 1994) IOP reduction in rabbits 12 hr after intravitreal injection of ET-1. Aqueous acetic acid (10ml glacial acetic acid in 100 ml water) was used as the diluent as described by Taniguchi (Taniguchi et al 1994) A 30 G needle, connected to PE60 polyethylene tubing and a microsyringe, was inserted transconjunctivally perpendicular to the globe through the pars plana 4 mm posterior to the limbus, to a depth of 4mm at the 10 (OD) or 2 o'clock (OS) position. AC and corneal fluorescence were measured hourly in both eyes over a 5 hr period (6 sets of scans) with a Coherent Fluorotron Master scanning ocular fluorophotometer (Topper 1984).…”

“…Indomethacin was ineffective at blocking the ET-1 IOP response following intravitreal injection, implying that endogenous prostaglandin release with a concomitant increase in uveoscleral and (in the case of rabbits) total outflow (Crawford & Kaufman 1987;Gabelt & Kaufman 1989;Nilsson et al 1989;Poyer et al 1992) was not involved in the IOP reduction (MacCumber et al 1991). Taniguchi and coworkers (Taniguchi et al 1994) found that after intravitreal injection of 0.5 mg ET-1 in rabbits, IOP initially rose for 1-2 hr then decreased for 96 hr. Twenty-four hr after injection, AHF measured fluorophotometrically was decreased by 58% (hypothesized as due to ET-mediated vasoconstriction of uveal vessels), total outflow facility measured by two-level constant pressure perfusion was increased by 94% (hypothesized as due to morphological changes in the outflow pathway induced by contraction of tissues around the chamber angle), and uveoscleral outflow determined by fluorescein-dextran perfusion was not significantly changed.…”