Prostaglandin F2α increases uveoscleral outflow in the cynomolgus monkey

doi:10.1016/0014-4835(89)90049-3

Experimental Eye Research

Volume 49, Issue 3, September 1989, Pages 389-402

https://doi.org/10.1016/0014-4835(89)90049-3 Get rights and content

Abstract

Cynomolgus monkeys were treated topically in one eye twice daily with prostaglandin F_2α-l-isopropylester (PGF_2α-IE) for nine doses. On treatment day 4, 3 hr after the seventh dose, intraocular pressure (IOP) in the treated eye was reduced by 65% compared to the controls, to < 5 mmHg. On treatment day 5, 3 hr after the ninth dose, total outflow facility was determined by two-level constant pressure perfusion of the anterior chamber. Immediately thereafter, uveoscleral outflow was determined by intracamerally infusing [¹²⁵I]- or [¹³¹I]-albumin and fluoresceinated dextran, and calculating the volume of anterior chamber fluid required to have deposited the quantity of tracer recovered from the various ocular and periocular tissues. Simultaneously, trabecular outflow was determined by calculating the volume of anterior chamber fluid required to have deposited the quantity of tracer recovered from the general circulation. Total facility was ∼ 50% higher in treated than in control eyes, but the effect was variable, of marginal statistical significance, and perhaps due to increased pseudofacility or uveoscleral facility. Uveoscleral outflow was approximately two to three-and-a-half times higher in treated than in control eyes, the magnitude of the effect being dependent upon the timing and pressure at which the perfusion was conducted. Trabecular outflow was reduced by ∼ 75% in the treated eyes relative to control so that the proportion of total outflow comprised by trabecular outflow in the treated eyes was only one third that in the controls. Total aqueous flow was slightly (∼ 20%) but not significantly reduced in the treated eyes. The IOP lowering effect of PGF_2α in the cynomolgus monkey is due largely if not exclusively to an increase in uveoscleral outflow of aqueous humor, with aqueous outflow being redirected from the trabecular to the uveoscleral route.

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Citation Excerpt :
However, where the fluid travels from here has been debated. Bill (Bill, 1966a; Bill and Phillips, 1971; Bill, 1975) and Gabelt and Kaufman (1989) postulate that the fluid seeps through sclera and episclera, and passes into the orbit where it is absorbed by the orbital vasculature (the uveoscleral pathway). Bárány (1967) and others (Pederson et al., 1977; Sherman et al., 1978) have proposed that a significant fraction of this fluid is absorbed osmotically by the choroid and passes into the vortex veins (the uveovortex pathway).
Aqueous humor flows out of the eye primarily through the conventional outflow pathway that includes the trabecular meshwork and Schlemm's canal. However, a fraction of aqueous humor passes through an alternative or ‘unconventional’ route that includes the ciliary muscle, supraciliary and suprachoroidal spaces. From there, unconventional outflow may drain through two pathways: a uveoscleral pathway where aqueous drains across the sclera to be resorbed by orbital vessels, and a uveovortex pathway where aqueous humor enters the choroid to drain through the vortex veins. We review the anatomy, physiology and pharmacology of these pathways. We also discuss methods to determine unconventional outflow rate, including direct techniques that use radioactive or fluorescent tracers recovered from tissues in the unconventional pathway and indirect methods that estimate unconventional outflow based on total outflow over a range of pressures. Indirect methods are subject to a number of assumptions and generally give poor agreement with tracer measurements. We review the variety of animal models that have been used to study conventional and unconventional outflow. The mouse appears to be a promising model because it captures several aspects of conventional and unconventional outflow dynamics common to humans, although questions remain regarding the magnitude of unconventional outflow in mice. Finally, we review future directions. There is a clear need to develop improved methods for measuring unconventional outflow in both animals and humans.

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^☆: Supported by National Eye Institute grant EY02698.

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Prostaglandin F2α increases uveoscleral outflow in the cynomolgus monkey☆

Abstract

Invest. Ophthalmol.

Arch. Ophthalmol.

Arch. Ophthalmol.

Exp. Eye Res.

Invest. Ophthalmol. Vis. Sci.

Intraocular pressure and ocular side effects after prostaglandin F2α eye drops. A single dose-response study in humans

Intraocular pressure and ocular side effects after prostaglandin F2α eye drops. A single dose-response study in humans

Simultaneous measurements of changing intraocular pressure and outflow facility in the vervet monkey by constant pressure infusion

Invest. Ophthalmol.

Conventional and uveo-scleral drainage of aqueous humor in the cynomolgus monkey (Macaca irus) at normal and high intraocular pressures

Exp. Eye Res.

The effect of changes in arterial blood pressure on the rate of aqueous humour formation in a primate (Cercopithecus ethiops)

Ophthalmic. Res.

Basic physiology of the drainage of aqueous humor

Long-term maintenance of reduced intraocular pressure by daily or twice daily topical application of prostaglandins to cat or rhesus monkey eyes

Invest. Ophthalmol. Vis. Sci.

Non-invasive observations on eyes of cats after long-term maintenance of reduced intraocular pressure by topical application of PGE2

Invest. Ophthalmol. Vis. Sci.

Reduction of intraocular pressure in normal and glaucomatous primate (Aotus trivirgatus) eyes by topically applied prostaglandin F2α

Curr. Eye Res.

Reduction of intraocular pressure by prostaglandins applied topically to the eyes of conscious rabbits

Invest. Ophthalmol. Vis. Sci.

Multiple dosing of prostaglandin F2α or epinephrine on cynomolgus monkey eyes. III. Histopathology

Invest. Ophthalmol. Vis. Sci.

Multiple dosing of prostaglandin F2α or epinephrine on cynomolgus eyes. I. Aqueous humor dynamics

Invest. Ophthalmol. Vis. Sci.

Pilocarpine antagonizes PGF2-induced ocular hypotension in monkeys. Evidence for enhancement of uveoscleral outflow by PGF2α

Arch. Ophthalmol.

Prostaglandin F_2α increases uveoscleral outflow in the cynomolgus monkey☆

Intraocular pressure and ocular side effects after prostaglandin F_2α eye drops. A single dose-response study in humans

Intraocular pressure and ocular side effects after prostaglandin F_2α eye drops. A single dose-response study in humans

Non-invasive observations on eyes of cats after long-term maintenance of reduced intraocular pressure by topical application of PGE₂

Reduction of intraocular pressure in normal and glaucomatous primate (Aotus trivirgatus) eyes by topically applied prostaglandin F_2α

Multiple dosing of prostaglandin F_2α or epinephrine on cynomolgus monkey eyes. III. Histopathology

Multiple dosing of prostaglandin F_2α or epinephrine on cynomolgus eyes. I. Aqueous humor dynamics

Pilocarpine antagonizes PGF₂-induced ocular hypotension in monkeys. Evidence for enhancement of uveoscleral outflow by PGF_2α