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Resting refractive correction in ketamine-, pentobarbital-, or halothane-anesthetized rhesus and cynomolgus monkeys was approximately 1-3 diopters myopic, with little difference under the various anesthetic regimens. Topical cyclopentolate or atropine, or systemic hexamethonium eliminated much of the myopia, while epinephrine, phenylephrine and thymoxamine had little effect. Anesthesia-induced myopia in monkeys thus seems comparable to tonic accommodation ("night myopia") in the human. Accommodation induced by electrical stimulation of the Edinger-Westphal nucleus averaged approximately 50% less under halothane than under pentobarbital, possibly due to halothane-induced systemic arterial hypotension.

The distribution of 3H and 14C activities in intraocular fluids and tissues was studied after topical application of 3H-prostaglandin F2 alpha (3H-PGF2 alpha) and/or 14C-arachidonic acid (14C-AA) to rabbit eyes; intravenous (i.v.) infusion of 3H-PGF2 alpha into rats; and after incubation of rat or rabbit globes in media containing these and other tracers. Thirty min after topical application of 14C-AA, the order of distribution of 14C per unit of tissue weight was cornea much greater than sclera congruent to ciliary body congruent to iris congruent to aqueous greater than retina-choroid greater than vitreous greater than lens. The distribution of 3H was sclera greater than cornea greater than retina-choroid congruent to ciliary body greater than aqueous greater than vitreous (lens congruent to 0; iris congruent to 0). After i.v. infusion of 14C-sucrose and 3H-PGF2 alpha into rats for 1 to 5 min, the globe/blood ratio of 3H was significantly lower than that of 14C. When isolated rat globes were incubated, the order of tracer uptake into the whole globe was AA greater than thiourea greater than PGF2 alpha greater than sucrose, while the order of entry into the aqueous was thiourea greater than sucrose greater than AA greater than -PGF2 alpha. The isolated rabbit cornea accumulated large amounts of 14C-AA which was not readily elutable and much smaller amounts of 3H-PGF2 alpha which was readily elutable. It is concluded that the sclera is highly permeable to PGF2 alpha, but that the cornea is an effective permeability barrier to this, and presumably all other PGs. The passage of AA through the outer coats of the globe is limited by its chemical incorporation into the cornea, sclera and conjunctiva. Thus, inhibition of the adverse intraocular effects of topically applied AA by topically applied drugs may only reflect the ability of these drugs to inhibit the synthesizing capacity of the superficial layers of the globe rather than that of the anterior uvea and other intraocular tissues.

The miotic potency of eleven naturally occurring polypeptides and poly-DL-alanine was tested on the isolated anterior segment of hooded rat and golden hamster eyes in order to gain information on the chemical nature of the peptides or classes of peptides which may be regarded as possible mediators of the miotic response of the mammalian eye to chemical irritants or mechanical or surgical trauma. Substance P, P-octapeptide, physalaemin and eledoisin, and eledoisin related peptide were found to be potent miotics on these preparations, yielding ED50 values in the range of 8 to 95 nM and complete pupillary constriction in the range of 100 to 1000 nM. This is comparable to the miotic potency of carbachol or serotonin. All of these peptides share a C-terminal sequence Phe-X-Gly-Leu-Met-NH2 (where "X" is a variable amino acid) which is characteristic of all tachykinins. Six other biologically active peptides or the synthetic poly-DL-alanine had no measureable miotic effect on these preparations up to a final concentration of 1000 to 10,000 nM. The miotic effect of SP on the rat iris was effectively, but not completely antagonized by the presence of 10(-7)M atropine sulfate in the incubation medium. Preliminary results indicate that the miotic effect of physalaemin, eledoisin and eledoisin related peptide on the anterior segment of rat eyes is similarly antagonized by atropine.

Topical application of a single dose of 1.0 mg prostaglandin F2 alpha (PGF2 alpha) onto the cornea of five trained owl monkeys (Aotus trivirgatus) caused a prolonged and highly significant ocular hypotony. The intraocular pressure (IOP) of the treated eye was 4.7 +/- 0.9 mm Hg below that of the control eye 18 to 24 hr after PGF2 alpha application and remained significantly reduced for over 72 hr. Miosis, aqueous flare, and accumulation of cells in the anterior chamber were minimal in extent. The hypotensive effect of PGF2 alpha was even more pronounced when applied to a glaucomatous owl monkey eye with angle recession, which had IOPs consistently in the 45 to 55 mm Hg range (mean: 47.2 +/- 0.7) as measured periodically over a one-year period. The application of a single dose of 1.0 mg of PGF2 alpha to this hypertensive eye reduced IOP by over 25 mm Hg within 4 hr, with a relative hypotony lasting for at least 6 days. These results show that topical application of certain PGs to normotensive or hypertensive primate eyes can cause a long lasting and highly significant decrease in IOP, and suggest that prostaglandins or their analogues may aid in the therapeutic control of ocular hypertension and glaucoma.

The effects of intravitreally injected prostaglandins (PGs) and arachidonic acid (AA) on the electrical activity of the retina were studied by monitoring the electroretinogram (ERG) of rabbits. In normal rabbits, intravitreal injection of PGE1, PGE2, or AA caused a gradual depression of b-wave amplitude as measured either in low (2 lux) or normal (300 lux) background illumination: up to 45% depression was observed within 1 hr and no recovery was noted during 4 hr of monitoring. The depression of the b-wave amplitude after the intravitreal injection of AA and PGs was similar in time course. Bromcresol green, an inhibitor of PG transport, significantly potentiated the effects of low doses of PGE1 and PGE2 and, to a lesser extent, that of AA. Indomethacin, a known inhibitor of cyclooxygenase activity, prevented the AA-induced, but not the PG-induced depression of the b-wave amplitude. It is concluded that PGs can have a direct effect on the retina and that this region of the eye contains sufficient cyclooxygenase activity to produce pathophysiologically significant amounts of PGs and/or related autacoids.

The concentration of copper [( Cu]) in the extracellular fluid compartments of rabbit eyes was found to increase approximately 30-fold during experimental uveitis, generally paralleling increases in [protein]. However, during the recovery phase the decrease in [Cu] lags behind the decrease in [protein] in some rabbits, suggesting the presence of abnormally high levels of non-protein-associated Cu. Intravitreal injection of CuSO4 (6 micrograms of Cu/eye) causes an inflammatory response and evidence of tissue damage. A better understanding of trace element metabolism is clearly required to further elucidate the mechanism of ocular inflammation and associated tissue damage.