Prostaglandin synthesis, inhibition, and intraocular pressure

Arachidonic acid, a precursor of prostaglandin E₂, administered topically to rabbit and monkey eyes in concentrations of 0.2 to 20%, or intravenously to rabbits in doses of 10 to 20 mg., produced a significant elevation of intraocular pressure. A dose response relationship was demonstrated. Facility of outflow and anterior chamber aqueous protein were significantly higher in eyes treated topically with 2% arachidonic acid than fellow control eyes. These effects of arachidonic acid were similar to those of prostaglandin E applied topically. Pretreatment with indomethacin, given intraperitoneally in doses of 10 mg. per kg. or greater, or aspirin, as a 600 mg. suppository, prevented completely the elevation of intraocular pressure produced by two drops of 2% arachidonic acid applied to the eyes of rabbits. The elevation of anterior chamber aqueous protein induced by topically applied 2% arachidonic acid also was blocked by prior administration of indomethacin. Indomethacin and aspirin, inhibitors of prostaglandin synthesis from arachidonic acid, had no effect on the rise of intraocular pressure seen after instilling 5 μg. of prostaglandins E₁ or E₂.