No abstract

To evaluate the effect of single or repeated topical applications of prostaglandin E₂ (PGE₂) to the cornea on the blood-aqueous barrier, we have measured the extent of flare in the anterior chamber of rabbit eyes at various time intervals. PGE₂ was applied to the cornea for 4 min with the use of a glass cylinder in pigmented rabbits. Aqueous flare was measured by a laser flare cell meter. The flare intensity following the second application of 25 or 50 μg/ml of PGE₂ was smaller than that following the first application. When 50 μg/ml of PGE₂ was applied every day for 6 days, the flare intensity decreased significantly day by day. After consecutive applications of 10 μg/ml of PGE₂ at hourly intervals, flare intensity increased up to 3 h, remained elevated from 3 to 5 h, and decreased thereafter. Repeated applications of 10 μg/ml of PGE₂, every hour for 14 h every Monday, significantly decreased flare intensity week by week. Weekly applications of 50 μg/ml of PGE₂ did not change flare intensity. This study indicates that the extent of the breakdown of the blood-aqueous barrier in the rabbit eye, as measured by the development of flare in the anterior chamber, is reduced with repeated PGE₂ application.

To evaluate the possible role of calcium channel blocker on changes in aqueous flare and intraocular pressure induced by prostaglandin E₂ (PGE₂) in pigmented rabbits, we examined the effects of nilvadipine and nicardipine (calcium channel blockers). PGE₂, 25 µg/ml, was administered using a glass cylinder. Nilvadipine or nicardipine was injected intravenously. Aqueous flare was measured by a laser flare cell meter. Intraocular pressure was measured by a noncontact tonometer. After administration of PGE₂, aqueous flare and intraocular pressure increased and then decreased. Increased flare and elevated intraocular pressure following PGE₂ administration were inhibited by nilvadipine in a dose-dependent manner (5–500 µg/kg body weight). These responses were inhibited only slightly by nicardipine at the same concentration. Nilvadipine injected 30 min before PGE₂ application inhibited the increase maximally. The inhibitory effect was found on days 1, 3, 5, and 7 by daily administration of nilvadipine. A good correlation between the inhibition of intraocular pressure and the inhibition of increased flare by nilvadipine was found. We believe that Ca²⁺, or calcium channel blocker-related substances may be involved in the mechanism of PGE₂-induced elevation of aqueous flare and intraocular pressure in the pigmented rabbit.

The purpose of this study was to examine the anti-inflammatory effect of the calcium channel blocker nicardipine. Intraocular inflammation was induced by argon laser photocoagulation of the iris of pigmented rabbits and was assessed by measuring aqueous flare and intraocular pressure. This resulted in a marked increase in the aqueous flare that peaked at approximately one hour following coagulation and returning to the original values after six hours. Intraocular pressure increased within 15 minutes following laser treatment and returned to baseline levels at 60 minutes. Pre-treatment of the rabbits with an intravenous injection of 2 mg/kg of nicardipine completely abolished both the increase in aqueous flare and intraocular pressure induced by laser photocoagulation as compared to the control experiment. Earlier work from the author's group has shown that nicardipine can also block aqueous flare and intraocular pressure increases induced by topical administration of prostaglandin E2. From these combined experiments they would like to draw the conclusion that the inflammatory reaction induced by photocoagulation of the iris is partly mediated by prostaglandins and that blockade of calcium channels by nicardipine can inhibit the effects induced by prostaglandin E2.

The effects of nilvadipine, nicardipine and verapamil on the acute rise of aqueous flare induced by argon laser photocoagulation of the iris or by intravenous injection of lipopolysaccharides (LPS, 0.5 µg/kg) were investigated in pigmented rabbits. Nilvadipine, nicardipine and verapamil were injected intravenously. Aqueous flare was measured with a laser flare cell meter. Following photocoagulation, aqueous flare increased, reached its maximum at 45–75 min and then decreased. After administration of LPS, aqueous flare increased, reached its maximum at 4 h and then returned to baseline levels at about 24 h. Flare reactions were inhibited by nilvadipine in a dose-dependent manner. The elevations were maximally inhibited by nilvadipine 30 min before photocoagulation or intravenous LPS. Two hundred micrograms per kilogram of nilvadipine inhibited 81% of photocoagulation-induced flare elevation, while the same dose of nicardipine and verapamil inhibited 19 and 9% of the elevation, respectively. The same dose of nilvadipine inhibited 51% of LPS-induced flare elevation, while the same dose of nicardipine and verapamil inhibited 6 and 4% of the elevation, respectively. In conclusion, nilvadipine inhibited the experimental elevation of aqueous flare more effectively than did nicardipine and verapamil.