The effect of topical natural ergot alkaloids on the intraocular pressure and aqueous humor dynamics in rabbits with α-chymotrypsin-induced ocular hypertension

BACKGROUND: We previously reported that topical natural ergot alkaloids ergocristine, alpha-ergocryptine and ergocornine dose-dependently reduce intraocular pressure in ocular normotensive rabbits, most likely by decreasing aqueous humor inflow. In the present study, the effects of these compounds on intraocular pressure and aqueous humor dynamics in a rabbit model for ocular hypertension were assessed. METHODS: Experiments were conducted in albino rabbits made ocular hypertensive by intracameral injection of alpha-chymotrypsin. Intraocular pressure responses to drug vehicle and seven different doses of topical natural ergot alkaloids were examined in order to obtain dose-response relationships for comparing the intraocular pressure-lowering effect and potency of these drugs. Tonographies were also performed to ascertain the actions of natural ergot alkaloids on aqueous humor dynamics in alpha-chymotrypsin-induced ocular hypertensive rabbits. RESULTS: Topical application of the natural ergot alkaloids ergocristine, alpha-ergocryptine and ergocornine lowered intraocular pressure in alpha-chymotrypsin-induced ocular hypertensive rabbits in a dose-related fashion, with ergocristine displaying the greatest intraocular pressure-lowering effect. Tonographic studies revealed a decrease in the tonographic outflow facility following topical application of natural ergot alkaloids, although only the effects of both ergocristine and alpha-ergocryptine reached statistical significance. All natural ergot alkaloids tested significantly reduced the calculated aqueous humor inflow. CONCLUSION: This study suggests that the natural ergot alkaloids ergocristine, alpha-ergocryptine and ergocornine effectively decrease intraocular pressure in the alpha-chymotrypsin-induced model of ocular hypertension. Since these compounds reduce the tonographic aqueous humor outflow facility, their final ocular antihypertensive effect appears to result from a remarkable reduction of the aqueous humor inflow.     

Effects of topical natural ergot alkaloids on intraocular pressure and aqueous humor dynamics in ocular normotensive rabbits.

Although it has been suggested that ergot derivatives may play a role in antiglaucoma therapy, little attention has been paid to the ocular hypotensive action of these drugs. Having previously reported in our laboratory that topical dihydroergocristine decreases intraocular pressure both in ocular normotensive and alpha-chymotrypsin-induced ocular hypertensive rabbits, the aim of the present work was to assess the effect of natural ergot alkaloids, ergocristine, alpha-ergocryptine and ergocornine, on the intraocular pressure and aqueous humor dynamics in ocular normotensive rabbits in order to further explore the ocular actions of these compounds. Intraocular pressure was measured with a pneumatonometer manometrically calibrated for the rabbit eye. Changes in tonographic facility of aqueous humor outflow and rate of aqueous humor inflow were evaluated in anesthetized rabbits. Natural ergot alkaloids were found to reduce intraocular pressure in ocular normotensive eyes in a dose-related fashion. These compounds decreased both tonographic outflow facility and, to a greater extent, aqueous humor inflow, which explains their final hypotensive effect.     

Topical verapamil lowers outflow facility in the rabbit eye.

Results of studies examining the mechanism of the ocular hypotensive effect of topical calcium channel blockers are controversial. Whereas evidence obtained in perfused human eyes indicates that these drugs lower intraocular pressure by increasing the aqueous humor outflow, tonographic studies in rabbits have revealed that they reduce both the aqueous humor outflow and inflow. In order to clarify such a discrepancy, the aim of this study was to assess whether the effect of topical verapamil on the facility of aqueous humor outflow in the rabbit eye was dose-related. Total outflow facility was determined by two-level constant pressure perfusion in anesthetized rabbits. The effect of 5 different concentrations on aqueous humor outflow at 60 minutes postdrug was studied in groups of 10 rabbits each. Baseline outflow facility was also determined in a group of 15 rabbits. In order to check the reliability of the method for detecting drug-induced changes in aqueous outflow, the effect of pilocarpine was also tested. Topical verapamil was shown to lower outflow facility in the rabbit eye in a dose-related fashion. On the contrary, topical pilocarpine was found to significantly increase outflow facility. Our data indicate that topical verapamil reduces outflow facility in the rabbit eye.     

A comparative study of topical natural ergot alkaloids on the intraocular pressure and aqueous humor dynamics in oclular normotensive and α-chymotrypsin-induced ocular hypertensive rabbits

Background Although it has been suggested that ergot derivatives may play a role in antiglaucoma therapy, little attention has been paid to the ocular hypotensive action of these drugs. Having previously reported that topical natural ergot alkaloids ergocristine α-ergocryptine and ergocornine dose-dependently reduce intraocular pressure in ocular normotensive and α-chymotrypsin-induced ocular hypertensive rabbits, the aim of the present work was to compare the effect of ergocristine, α-ergocryptine and ergocornine on the intraocular pressure and aqueous humor dynamics in ocular normotensive and α-chymotrypsin-induced ocular hypertensive rabbits, in order to further explore the ocular actions of these compounds. Methods Experiments were conducted in albino ocular normotensive and hypertensive rabbits by intracameral injection of α-chymotrypsin. Intraocular pressure responses to drug vehicle and seven different doses of topical natural ergot alkaloids were examined, in order to obtain dose–response relationships for comparing the intraocular pressure-lowering effect and potency of these drugs. Tonographies were also performed to ascertain the actions of natural ergot alkaloids on aqueous humor dynamics. Results All natural ergot alkaloids tested reduced intraocular pressure in a dose-related fashion. The ocular hypotensive effect was greater in α-chymotrypsin-induced ocular hypertensive rabbits for the three compounds tested. All natural ergot alkaloids tested decreased both tonographic outflow facility and, to a greater extent, aqueous humor inflow in ocular normotensive and in α-chymotrypsin-induced ocular hypertensive rabbits. Conclusion Taken together, our data suggest that these compounds decrease both tonographic outflow facility and, to a greater extent, aqueous humor inflow, which explains their final effect in ocular normotensive and in α-chymotrypsin-induced ocular hypertensive rabbits. Reductions in aqueous humor inflow observed after topical application of natural ergot alkaloids in α-chymotrypsin-induced ocular hypertensive rabbits can only be explained by a marked inhibition of active secretion of aqueous humor, since processes involved in aqueous humor formation may probably be altered after α-chymotrypsin injection.     

The effect of topical CS-088, an angiotensin AT1 receptor antagonist, on intraocular pressure and aqueous humor dynamics in rabbits

PURPOSE: To evaluate the ocular hypotensive effect of topical CS-088, an angiotensin AT1 receptor antagonist, and the effect of CS-088 on aqueous humor dynamics. METHODS: The effects of CS-088 on intraocular pressure (IOP) were studied in 2 models of rabbit ocular hypertension. Experimental ocular hypertension was induced in albino rabbits by injecting alpha-chymotrypsin into the anterior chamber (alpha-chymotrypsin rabbit). The effects of the single application of CS-088 were examined. Additionally, CS-088 was repeatedly administered over a period of 3 weeks to hereditary ocular hypertensive rabbits (buphthalmic rabbits, JWHR bu/bu) and the IOPs were monitored throughout the experiment. The effects of CS-088 on aqueous humor dynamics were also examined in normal rabbits. In this study, the methods of IOP recovery rate, two-level constant pressure perfusion and fluorescein-dextran perfusion were used respectively to determine the aqueous inflow, outflow facility and uveoscleral outflow (USF). RESULTS: CS-088 at 1% and 2% significantly lowered the IOP in the alpha-chymotrypsin rabbits with a maximum IOP reduction of 10.1 mmHg. The maximum effect obtained with 2% CS-088 was no greater than that with 1% CS-088. In the buphthalmic rabbits, 2% CS-088 also lowered IOP significantly. Timolol was effective in both models. In the study on aqueous humor dynamics, a slight increase in USF (17%) was seen after a topical application of CS-088 whereas changes in aqueous inflow or outflow facility were not observed. CONCLUSIONS: Topical CS-088 can decrease IOP in rabbits. Despite the USF change, the ocular hypotensive mechanism by CS-088 was not fully determined.     

Effects of brinzolamide on aqueous humor dynamics in monkeys and rabbits.

This study examines the mechanisms by which brinzolamide reduces intraocular pressure (IOP) in healthy rabbits and in monkeys with unilateral ocular hypertension. Intraocular pressures were measured by pneumatonometry and aqueous flow was determined by fluorophotometry before and after three twice-daily drops of 1% brinzolamide to both eyes per monkey and after similar treatment to one eye per rabbit. In monkeys, outflow facility was determined by fluorophotometry and uveoscleral outflow was calculated. In rabbits, outflow facility was determined by two-level constant pressure infusion and uveoscleral outflow was measured by an intracameral tracer technique. Compared with contralateral vehicle-treated rabbit eyes, IOP was reduced in brinzolamide-treated eyes by 2.5 +/- 1.9 mmHg (mean +/- standard deviation; p =.006) at four hours after the second dose. Aqueous flow was reduced by 0.50 +/- 0.65 microl/min (p =.02). This effect was found in rabbits previously treated with brinzolamide but not in naive rabbits. Treated hypertensive eyes of monkeys had a reduction in IOP of 7.3 +/- 8.8 mmHg (p = 0.01) and aqueous flow of 0.69 +/- 1.10 microL/min (p = 0.05) when compared with baseline. Brinzolamide did not affect outflow facility or uveoscleral outflow in either rabbits or monkeys. It is concluded that, in normotensive eyes of rabbits and hypertensive eyes of monkeys, brinzolamide reduces IOP by reducing aqueous flow and not by affecting aqueous humor drainage.     

A fluorophotometric study on the aqueous humor dynamics in primary open angle glaucoma

One hundred and ten eyes in 40 normal persons with no ocular pathology, 20 with ocular hypertension and 50 with primary open angle glaucoma were studied. The value of the aqueous humor flow was obtained and then compared with the different samples and with general (age, sex) and ocular factors (intraocular pressure, tonographic outflow facility, campimeter and disk/cup ratio, among others.     

The effect of betablockers with and without ISA on tonographic outflow facility

Summary The response of two ophthalmic betablockers, Timolol (without ISA) and Pindolol (with marked ISA), on IOP and tonographic outflow facility was investigated in a single-blind clinical study on 20 patients with glaucoma or ocular hypertension. In two treatment groups, ten patients each, in a randomized order IOP and tonographic outflow facility measurements were performed before and 2 hrs after drug application. Timolol reduced IOP by 6,8 mm Hg and Pindolol eye drops by 4,5 mm Hg. Both topically applied betablockers did not influence tonographic facility of outflow. It is concluded that the intrinsic sympathomimetic activity of an ophthalmic betablocker has no effect on outflow facility of aqueous humor.     

Effects of topical epinephrine on aqueous humor dynamics in the cat

The purpose of this study was to investigate, in cats, the effects of topical epinephrine on aqueous humor dynamics as measured by the non-invasive method of fluorophotometry and by other methods. Measurements were carried out on 12 cats before and after one week of twice daily treatment with 2% epinephrine hydrochloride to one eye. Aqueous flow and outflow facility were determined using fluorophotometry. Uveoscleral outflow was calculated from these results and was evaluated with anterior chamber perfusion of FITC-dextran. Outflow facility also was measured by tonography. Epinephrine-treated eyes, compared with their baseline values, showed a 31% reduction in intraocular pressure (P<0.001), a 23% reduction in aqueous flow (P<0.05), a 60% increase in fluorophotometric outflow facility (P<0.05), and a 43% increase in tonographic outflow facility (P<0.05). Treated eyes, compared with contralateral control eyes, showed a 27% reduction in IOP (P<0.005), a 25% reduction in aqueous flow (P<0.005), a 38% increase in fluorophotometric outflow facility (P<0.05), and a 34% increase in tonographic outflow facility. When evaluated by both fluorophotometry and FITC-dextran tracer methods, epinephrine had no significant effect on uveoscleral outflow. It was concluded that, in cats treated with topical epinephrine twice daily for a week, a reduction in intraocular pressure is induced by an increase in outflow facility and decrease in aqueous flow.     

Effects of AGN 192024, a new ocular hypotensive agent, on aqueous dynamics

PURPOSE: To determine the mechanism of intraocular pressure lowering for the Ocular Hypotensive Lipid, AGN 192024 (Allergan, Inc, Irvine, California). METHODS: Twenty-five normal human volunteers between the ages of 21 and 48 took part in a randomized, double-masked, placebo-controlled, paired-comparison study in which intraocular pressure, aqueous humor flow, and tonographic resistance to outflow were studied. Measurements of aqueous flow were made during the day and at night while subjects slept. Intraocular pressure was measured with the Goldmann tonometer, and resistance to outflow was measured by electronic recording Schi?tz tonography. RESULTS: Intraocular pressure was decreased by 20% on day 3 in AGN 192024-treated eyes in comparison with placebo-treated eyes in normal subjects (P <.001). Aqueous humor flow was stimulated 13% during the day (P =.007) and 14% at night (P =.014) by the drug. Tonographic resistance to outflow was decreased 26% by AGN 192024 (P <.001), and apparent resistance to outflow (the ratio of intraocular pressure to aqueous flow) was decreased 31% (P <.001). Assuming that AGN 192024 does not cause prolonged lowering of episcleral venous pressure, the results show that pressure-insensitive outflow is enhanced by 50%, whereas tonographic facility of outflow (reciprocal of resistance) was enhanced 35%. CONCLUSIONS: AGN 192024 is an ocular hypotensive agent that works by enhancing both pressure-sensitive and pressure-insensitive aqueous humor outflow without diminishing aqueous humor formation.     

Topical vanadate lowers intraocular pressure in rabbits

In unanesthetized rabbits the topical application of vanadate lowered intraocular pressure. Tonographic outflow facility and episcleral venous pressure were unaltered by topical vanadate. As estimated from the tonographic data, aqueous humor flow was reduced by approximately 30%. Posterior chamber aqueous humor ascorbate increased in the eye receiving topical vanadate, and this was compatible with a decreased rate of aqueous humor flow. Topical vanadate did not alter anterior chamber aqueous humor protein or cyclic AMP. In five monkeys intraocular pressure was also significantly reduced by topical vanadate.     

Aqueous humor dynamics in mice

PURPOSE: To assess aqueous humor dynamics in mouse eyes. METHODS: Aqueous humor dynamics of NIH Swiss White mouse were assessed with an injection and aspiration system, using fine glass microneedles. Intraocular pressure (IOP) was measured by a microneedle connected to a pressure transducer. Episcleral venous pressure (EVP) was measured by gradually lowering intracameral pressure until blood reflux into Schlemm's canal was observed. Outflow facility (C) was determined based on constant pressure perfusion measurements obtained at two different IOPs. Aqueous volume (V(a)) was determined by direct measurement of aspirated aqueous humor. Aqueous humor production (F(a)) was measured by the dilution method with rhodamine-dextran. Conventional and uveoscleral outflow (F(c) and F(u), respectively), as well as the turnover rate of aqueous humor, were also calculated. RESULTS: IOP and EVP were 15.7 +/- 2.0 and 9.5 +/- 1.2 mm Hg, respectively (n = 20). F(a) was 0.18 +/- 0.05 microL/min (mean +/- SD; n = 8). C was 0.0051 +/- 0.0006 microL/min per mm Hg (n = 8). Estimated F(c) and F(u) were 0.032 and 0.148 microL/min, respectively. F(c) was 18% of F(a). F(u) was 82% of F(a). V(a) was 5.9 +/- 0.5 microL (n = 8). The calculated turnover rate of aqueous humor was 2.5%. CONCLUSIONS: The mouse eye has similar aqueous production and aqueous humor turnover rate as the human eye. The presence of both conventional and uveoscleral outflow suggests that the mouse is a useful model system for further investigations of the biology of aqueous dynamics.     

Effects of topical nipradilol, a beta blocking agent with alpha blocking and nitroglycerin-like activities, on intraocular pressure and aqueous dynamics in humans

AIMS: To study the effects of topical nipradilol, a non-selective beta blocker with alpha blocking and nitroglycerin-like activities, on intraocular pressure (IOP) and aqueous humour dynamics in normal humans and in patients with ocular hypertension. METHODS: Nipradilol (0.06%, 0.125%, 0.25%, 0.5%) was applied to normal volunteers (n = 12) to test for IOP lowering effects. In a second group of normal volunteers (n = 11), nipradilol (0.125% and 0.25%) and timolol (0. 5%) were compared for IOP lowering effects. After a single administration of 0.25% nipradilol, IOP, flare intensity in the anterior chamber, aqueous flow, uveoscleral outflow, tonographic outflow facility, and episcleral venous pressure were either directly measured or mathematically calculated. Topical nipradilol (0.25%) was administered to 24 patients with ocular hypertension twice daily for 8 weeks. RESULTS: Administration of 0.25% nipradilol decreased IOP with a maximum reduction of 4.2 mm Hg lasting 12 hours. A single instillation of both 0.25% nipradilol and 0.5% timolol reduced the IOP in normotensive human subjects to the same degree. A single instillation of 0.25% nipradilol decreased the aqueous flow rate in the treated eye by 20%. Nipradilol produced no significant effect in tonographic outflow facility or episcleral venous pressure, but uveoscleral outflow was increased. In patients with ocular hypertension, twice daily instillation of 0.25% nipradilol decreased IOP without tachyphylaxis for the 8 week test period. CONCLUSION: Topical nipradilol (0.25%) reduced IOP by decreasing the aqueous flow rate and probably also by increasing uveoscleral outflow. Nipradilol should be further investigated as a new antiglaucoma drug.     

The prostanoid EP2 receptor agonist butaprost increases uveoscleral outflow in the cynomolgus monkey

PURPOSE: To investigate the ocular hypotensive effect of the prostanoid EP2 receptor agonist butaprost and to establish its mechanism of action. METHODS: All experiments were performed in cynomolgus monkeys after topical application of butaprost (0.1%). The effects of butaprost on aqueous humor flow were determined by fluorophotometry. Total outflow facility was measured by the two-level, constant-pressure perfusion method, and uveoscleral outflow was determined by perfusion of FITC-labeled dextran through the anterior chamber. Effects on ocular morphology were studied after tissue fixation with transcardial perfusion by paraformaldehyde and immersion fixation of the globe, in animals subjected to long-term treatment with butaprost. Conscious ocular normotensive monkeys and monkeys with unilateral ocular hypertension were used for intraocular pressure (IOP) studies. RESULTS: Butaprost had no significant effect on aqueous humor flow or total outflow facility in ocular normotensive monkeys. Uveoscleral outflow was significantly higher in the butaprost treated eyes than in vehicle treated eyes, 1.03 +/- 0.20 vs. 0.53 +/- 0.18 microL.min(-1). After a 1-year treatment with butaprost, the morphology of the ciliary muscle was changed, showing increased spaces between ciliary muscle bundles and the apparent formation of new outflow channels. In many instances, changes were observed in the trabecular meshwork as well. Butaprost, in a single 0.1% dose, decreased IOP significantly in ocular normotensive monkeys and reduced IOP in laser-induced glaucomatous monkey eyes to the same level as that in the ocular normotensive contralateral eyes. CONCLUSIONS: The prostanoid EP2 receptor agonist butaprost appears to lower IOP by increasing uveoscleral outflow, according to both physiological and morphologic findings. Although the prostanoid EP2 receptor is structurally and functionally distinct from the FP receptor, the effects of EP2 and FP receptor stimulation on aqueous humor outflow are similar.     

Aqueous humor dynamics in ocular hypertensive patients

PURPOSE: To evaluate the mechanism of the intraocular pressure (IOP) elevation in ocular hypertension (OHT), aqueous humor dynamics were compared in patients with OHT versus age-matched ocular normotensive (NT) volunteers. METHODS: In this retrospective study, one group included patients diagnosed with OHT (IOPs > 21 mm Hg, n = 55) for at least six months. All eye medications were discontinued for at least three weeks before the study visit. A second group included age-matched NT subjects (n = 55) with no eye diseases. The study visit included measurements of IOP by pneumatonometry, aqueous flow and outflow facility by fluorophotometry, anterior chamber depth and corneal thickness by pachymetry and episcleral venous pressure by venomanometry. Uveoscleral outflow and anterior chamber volume were calculated mathematically. RESULTS: Significant differences in the OHT versus the NT groups were as follows: increased IOP (21.4 +/- 0.6 versus 14.9 +/- 0.3 mm Hg, respectively; P < 0.0001), reduced uveoscleral outflow (0.66 +/- 0.11 versus 1.09 +/- 0.11 microL/min; P = 0.005) and reduced fluorophotometric outflow facility (0.17 +/- 0.01 versus 0.27 +/- 0.02 microL/min/mm Hg; P < 0.0001). With respect to age, anterior chamber volume decreased in both groups at a rate of 2.4 +/- 0.3 microL/year (r(2) = 0.5, P <.001) and aqueous flow decreased at a rate of 0.013 +/- 0.005 microL/min/year (r(2) = 0.07, P = 0.005). CONCLUSIONS: The increased IOP in ocular hypertensive patients is caused by a reduction in trabecular outflow facility and uveoscleral outflow. Aqueous flow remains normal. When both ocular normotensive and hypertensive groups are combined, aqueous flow and anterior chamber volume decrease slightly with age.     

Effects of a cyclic AMP phosphodiesterase inhibitor, 8'-pivaloyloxymethyl ester of griseolic acid, on aqueous humor dynamics in rabbits.

The mechanism by which pivaloyloxymethyl (POM) ester of griseolic acid (GA), a potent cyclic AMP-phosphodiesterase inhibitor, lowers intraocular pressure (IOP) in albino rabbits was studied. The rate of aqueous flow, measured by fluorophotometry, was significantly lower in GA POM ester-treated eyes (2.36 +/- 0.24 microliters/min) than in control eyes (3.02 +/- 0.24 microliters/min). Topically applied GA POM ester did not alter tonographic outflow or uveoscleral outflow. No differences in aqueous humor protein concentrations between GA POM ester-treated and control eyes were observed. It was thought that the GA POM ester lowered the IOP by decreasing the aqueous inflow. Topical application of this compound caused no inflammatory response in the eye or changes in the blood aqueous barrier.     

The effect of topical PGF2 alpha on uveoscleral outflow and outflow facility in the rabbit eye.

Prostaglandin F2 alpha (PGF2 alpha) is a powerful ocular hypotensive agent in rabbit, cat, dog, monkey and human. In cynomolgus monkeys, the intraocular pressure (IOP) lowering is due to increased uveoscleral outflow (Fu). Because the anatomy of the rabbit outflow apparatus differs significantly from that of the primate, we sought to determine whether the mechanism of the PGF2 alpha-induced IOP fall was the same. PGF2 alpha tromethamine salt (PGF2 alpha-TS) (50 micrograms) applied to one eye of 14 conscious rabbits produced a significant IOP fall of 7.4 +/- 0.9 mmHg (P less than 0.001). In untreated control eyes, Fu determined from the quantity of intracamerally perfused [125I]albumin found in the ocular and periocular tissues accounted for 5-8% of total aqueous outflow. In 15 unilaterally PGF2 alpha-treated rabbits, after 4-6 hr dosing Fu was 49 +/- 14% higher in the treated than in the contralateral control eyes. Total outflow facility of outflow from the anterior chamber to the general circulation were measured concurrently in 11 rabbits using a two-level constant pressure perfusion and isotope accumulation technique. Both facilities tended to be higher in the treated eyes than in the controls, with a strong correlation between drug-induced changes in total facility and changes in facility of flow to blood (r = 0.85, P less than 0.001). In eight rabbits treated unilaterally with 50 micrograms PGF2 alpha-TS, the fluorophotometrically determined aqueous formation rate was probably not decreased relative to control eyes. Protein levels in the aqueous humor were approximately eight-fold higher in PG-treated vs. control eyes, suggesting a drug-induced compromise of the blood-aqueous barrier.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of topical PGF2 alpha on aqueous humor dynamics in cynomolgus monkeys

Single topical applications of prostaglandin F2 alpha (PGF2 alpha) tromethamine salt to living cynomolgus monkey eyes reduced intraocular pressure (IOP). Twice daily topical application was far more effective, so that after the 7th 50 micrograms or 100 micrograms dose on day 4, IOP fell 40-50%, to 8-10 mm Hg. Following twice daily application of 50 or 100 micrograms for greater than 3 days: (1) no increase in total outflow facility could be demonstrated by 2-level constant pressure perfusion or Schiotz tonography; (2) no decrease in aqueous humor formation rate could be demonstrated by fluorophotometry--rather, aqueous flow may have increased; (3) anterior chamber aqueous humor protein concentration was unaltered, but entry of intravenously injected fluorescein into the cornea and anterior chamber tended to increase; (4) there was a weak but sometimes statistically significant miosis of up to approximately 0.5 mm. We conclude that in the cynomolgus monkey: (1) PGF2 alpha is a potent ocular hypotensive agent with only very weak miotic and blood-aqueous barrier-disrupting effects; (2) the ocular hypotensive action of PGF2 alpha is definitely not due to increased conventional outflow facility or decreased aqueous production, but probably to increased uveoscleral drainage of aqueous humor.     

Aqueous humor dynamics in the aging human eye

PURPOSE: Healthy subjects were recruited to identify normal, age-associated changes in intraocular pressure and aqueous humor dynamics. METHODS: Normal healthy subjects from two age groups were enrolled in the study: (1) those from 20 to 30 years of age (n = 51) and (2) those 60 years of age and older (n = 53). Intraocular pressure was measured by pneumatonometry, tonographic outflow facility by pneumatonography, and episcleral venous pressure by venomanometry. Aqueous flow and outflow facility were determined by a fluorophotometric technique. Uveoscleral outflow and anterior chamber volume were calculated. Results from the older group were compared with those from the younger group by means of unpaired, two-tailed t tests. RESULTS: Compared with the younger group, the older group showed significant differences as follows: smaller anterior chamber volume (160+/-39 vs. 247+/-39 microl; mean +/- SD; P< .00001), reduced aqueous flow (2.4+/-0.6 vs. 2.8+/-0.8 microl/minute; P = .002), and reduced uveoscleral outflow (1.10+/-0.81 vs. 1.52+/-0.81 microl/minute; P = .009). CONCLUSIONS: In the healthy aging eye, there is a reduction in the production of aqueous humor and a reduction in its drainage through the uveoscleral outflow pathway.     

Eicosanoids as a new class of ocular hypotensive agents. 2. Comparison of the apparent mechanism of the ocular hypotensive effects of A and F type prostaglandins

It has recently been shown that derived prostaglandins (PGs) of the A and B types are much more potent ocular hypotensive agents than primary PGs of the E, F, or D type. The purpose of this study was to determine whether two representatives of these structurally different PGs, namely PGA2 and PGF2 alpha-1-isopropyl ester (PGF2 alpha IE), reduce intraocular pressure (IOP) of the feline eye by similar or dissimilar mechanisms. Aqueous humor flow rate was determined by a fluorophotometric technique, Schiotz electronic tonography was used to measure outflow facility and venomanometry was done to measure episcleral venous pressure. Although at the doses used, both PGF2 alpha IE (2.5 micrograms/eye) and PGA2 (5.0 micrograms/eye) caused significant IOP reduction within 2.5 hr after their topical application, neither caused a significant decrease in aqueous humor flow rate, a significant increase in outflow facility or a change in episcleral venous pressure. It was concluded, therefore, that both of these PGs reduce IOP by an apparently similar mechanism, presumably by increasing uveoscleral outflow.