Effects of serotonergic compounds on aqueous humor dynamics in monkeys

PURPOSE: The effects of several serotonergic agonists on aqueous humor formation (AHF), total outflow facility (OF) and intraocular pressure (IOP) were investigated in living cynomolgus monkeys. METHODS: We determined the effect of a single topical unilateral 300 microg or 3 mg dose of the 5-HT agonists serotonin, 5-carboxamidotryptamine (5-CT), sumatripan, gepirone, and 8-hydroxy-2(di-n-propylaminotetralin) (8-OH-DPAT) and a 450 microg dose of flesinoxan on IOP (Goldmann applanation tonometry), AHF (scanning ocular fluorophotometry) and total OF (8-OH-DPAT only, topically and intracamerally). RESULTS: Serotonin, 5-CT, sumatripan or gepirone had no significant effect on IOP or AHF. 8-OH-DPAT caused an AHF increase of approximately 70% over 6 hr in both ipsilateral drug- and contralateral vehicle-treated eyes, but no significant change in IOP compared with baseline measured on a separate occasion in the same animals. 8-OH-DPAT did not increase protein levels or rate of entry of systemically administered fluorescein in the anterior chamber aqueous humor compared to historic controls, and no difference was seen between ipsilateral and contralateral eyes. Flesinoxan had no effect on IOP and produced an insignificant 25% increase in flow in treated eyes compared to baseline. CONCLUSION: The results for 8-OH-DPAT and possibly flexinoxan indicate the presence of a secretion-stimulating 5-HT1A receptor in monkey ciliary epithelium that has little effect on IOP. OF was unchanged following 8-OH-DPAT administered topically or following intracameral exchange.     

Unoprostone isopropyl pretreatment decreases endothelin-1 release and the intra-ocular pressure spike induced by laser trabeculoplasty in the rabbit

PURPOSE: We have previously shown that the intra-ocular pressure (IOP) spike due to argon laser trabeculoplasty (ALT) is caused by an acute endothelin-1 (ET-1) release from the uveal tissue into the aqueous humour of rabbit eyes. In this study we investigated whether pretreatment with topical unoprostone isopropyl, a functional antagonist of ET-1, protects against the pressure spike due to ALT in the rabbit model. METHODS: IOP of both eyes of 17 pigmented rabbits was measured with a TonoPen XL tonometer under general anaesthesia (baseline measurement). Then the right eyes were treated with topical unoprostone isopropyl 0.12% BID for 6 days, and the left eyes similarly received balanced salt solution (BSS) twice daily. After the last morning instillation, IOP for both eyes was measured under general anaesthesia after 2 h in group 1 and after 3 h in group 2 animals. Then, for both groups, ALT was performed on both eyes. Thirty minutes after laser treatment (and still under general anaesthesia), IOP was measured again. Then the aqueous humour was aspirated for measurement of ET-1 concentration. RESULTS: Baseline individual IOP differences (left eye minus right eye) were not significant in both groups: mean +/- SD 0.25 +/- 1.16 and -0.33 +/- 0.71 mm Hg, respectively (paired t test, p > 0.05 for both groups). On day 6, 2 h (group 1) and 3 h (group 2) after the last instillation but before laser trabeculoplasty, the difference (BSS-pretreated left eye minus unoprostone-pretreated right eye) increased to 2.13 +/- 2.10 mm Hg (p = 0.024) and 1.33 +/- 0.71 mm Hg (p = 0.0005), respectively. Thirty minutes after ALT, the IOP difference was 2.63 +/- 2.67 mm Hg in group 1 (p = 0.027), but no difference was seen in group 2 (0.67 +/- 1.94 mm Hg, p = 0.332). In group 1, postoperative aqueous humour ET-1 concentration for the unoprostone-pretreated right eye was significantly lower than that for the BSS-pretreated left eye (paired t test, p = 0.01); but in group 2 no inter-ocular difference in ET-1 concentration was found (p = 0.976). CONCLUSION: Topical unoprostone pretreatment decreases laser-induced ET-1 release and diminishes the IOP spike caused by ALT in vivo within 2 h after instillation, when the concentration of unoprostone in the aqueous humour is high.     

Different Effects of Topical Prazosin and Pilocarpine on Uveoscleral Outflow in Rabbit Eyes

Purpose:To investigate the effects of topical prazosin and pilocarpine on uveoscleral outflow(Fu) in rabbits.Methods:Sixteen rabbits were randomly divided into the control group (5 rabbits, only topical application of normal saline in the fight eye of each rabbit), Prazosin (PZ) treated group (6 rabbits, only 0.1％ Prazosin eyedrop 0.1％ in the right eye of each one) and Pilocarpine (PC) treated group (5 rabbits, 1％ Pilocarpine eye drop in each fight eye). Intraocular pressure (IOP) of bilateral eyes of each rabbit was measured before and 1h after topical application of the eye drop. And the bilateral eyes were perfused with Fluorescein-isothiocyanate bovine serum albumin (FITC-BSA) as the tracer into the anterior chamber of each rabbit for 30 min at 90 min after topical treatment. Then the rabbits were killed for Fu measurement.Results:IOP of PZ-treated eyes decreased [(0.71±0.07)kPa] in 1 hour after PZ application. IOP of PC-treated eyes decreased [(0.70±0.08)kPa] in 1 hour after PC application. Th     

Immediate increase in aqueous humour endothelin 1 concentration and intra-ocular pressure after argon laser trabeculoplasty in the rabbit

PURPOSE: To investigate the immediate changes of aqueous humour endothelin 1 (ET-1) concentration and intra-ocular pressure (IOP) after argon laser trabeculoplasty (ALT) in the rabbit. METHODS: Standard ALT was performed in one eye of 11 pigmented rabbits. IOP was measured with a Tono-Pen-2 tonometer before treatment, under general anaesthesia. Postlaser IOP measurements followed by aqueous humour aspiration were performed under general anaesthesia 30 and 60 min after treatment in 6 and in 5 animals, respectively. RESULTS: The aqueous humour ET-1 concentration was significantly higher (55.0 pg/ml) after ALT than in the contralateral eyes without laser treatment (8.2 pg/ml, p = 0.001). IOP increased significantly after ALT (p = 0.007) but remained unaltered (p = 0.10) in the contralateral eyes without treatment. No statistically significant difference was found either in postlaser IOP elevation or in interocular ET-1 difference between the groups. CONCLUSIONS: The results suggest that in the rabbit the increase in aqueous humour ET-1 concentration after ALT is immediate, detectable even 30 min after the laser treatment, followed by no further increase during the second 30-min period after ALT, and associated with an immediate postlaser IOP elevation within 1 h after ALT. These findings may suggest a similar response to ALT in the human eye, since a similar immediate IOP elevation is frequently observed after ALT in the clinical practice.     

Endothelin-A receptor antagonist BQ-485 protects against intraocular pressure spike induced by laser trabeculoplasty in the rabbit

PURPOSE: We have previously shown in rabbits that the intraocular pressure (IOP) spike caused by argon laser trabeculoplasty (ALT) is associated with an acute endothelin-1 (ET-1) release from the uveal tissue into the aqueous humour. In this study we investigated whether pretreatment with an ET(A) receptor antagonist (BQ-485) protects against the pressure spike induced by ALT, in the rabbit model. METHODS: Under general anaesthesia, 10 microl of 10(-5) M BQ-485 was injected into the anterior chamber of the right eye, and 10 microl of balanced salt solution (BSS) into the contralateral anterior chamber, for 12 pigmented rabbits. Five minutes later ALT (1,000 mW, 0.1 s, 100 spots over 360 degrees focused on the iris pillars) was performed on both eyes of each animal. IOP was measured before the injections (baseline value), and also 30 min afterwards using a Tono-Pen XL tonometer. Immediately after the second IOP measurement aqueous humour was aspirated for measurement of ET-1 concentration. RESULTS: The baseline IOP (mean +/- SD) was 8.08 +/- 1.73 mm Hg and 7.92 +/- 1.78 mm Hg for the right and left eyes, respectively (Duncan test, p > 0.05). At 25 min after ALT the IOP of the BQ-485-pretreated right eyes remained unchanged (7.83 +/- 2.44 mm Hg, p > 0.05) but the IOP of the BSS-pretreated left eyes at 30 min increased significantly to 10.67 +/- 4.70 mm Hg (p < 0.05 for comparisons both with the corresponding baseline value for the same eye, and with the IOP of the contralateral eye at 30 min). There was no difference in aqueous humour ET-1 concentration between the corresponding right and left eyes (paired t test, p > 0.05). CONCLUSION: Intracameral BQ-485 pretreatment protected against the ALT-induced acute IOP elevation, but did not influence the laser-induced ET-1 release. This suggests that ET(A )receptor antagonists may potentially have a therapeutic role in the prevention of laser-induced IOP spikes.     

Relationship between the concentration of copper and iron in the aqueous humour and intraocular pressure in rabbits treated with topical steroids

Purpose: To evaluate the concentration of copper and iron in the aqueous humour of steroid‐treated eyes, particularly to study the concentration of these metals in relation to steroid‐induced increases in intraocular pressure (IOP). Methods: Adult rabbits of both sexes were selected in order to study the effect of steroids on the concentrations of copper and iron in the aqueous humour and on IOP. The rabbits were acclimatised for 2 weeks prior to the instillation of various drugs into the eyes. Then a steroid (dexamethasone, betamethasone or fluoromethalone) was instilled in both eyes of the rabbits, for about 1 month. Intraocular pressure was measured twice a week. When IOP was significantly increased, the animals were killed. The aqueous humour was collected and analysed for copper and iron using atomic absorption spectrophotometry coupled with graphite furnace. Results: After about 30 days of steroid treatment the mean (± SD) IOP in dexamethasone, betamethasone and fluoromethalone treated groups was 17.5 (± 4.81) mmHg, 18.48 (± 4.5) mmHg and 21.8 (± 5.7) mmHg, respectively. These values were significantly higher compared to the control group where the mean IOP was 11.6 (± 2.2) mmHg. The concentration of copper in the aqueous humour of steroid‐treated rabbits was significantly lower (P < 0.001) compared to the control group. However, the concentration of iron was not significantly different between the control and steroid treated rabbits. Conclusion: A greater increase in IOP was observed in the fluoromethalone‐treated group compared to the dexa­methasone and betamethasone‐treated groups, but the difference was not significant. The lower concentrations of copper in aqueous humour in steroid‐treated eyes may play an important role in the maintenance of IOP. The concentration of iron was not significantly different compared to the control group. These results may help to explain the role of these metals in the pathogenesis of open angle glaucoma.     

8OH-DPAT-Induced ocular hypotension: sites and mechanisms of action.

The purpose of this study was to define the ocular actions of 8-OH-DPAT(DPAT), a 5-HT(1A)receptor agonist. The intraocular pressure responses to topically applied DPAT were dose related (25, 125, 250 microgram) and bilateral in normal rabbits but of relatively short duration. Ocular hypotension induced by topical, unilateral DPAT (125 microgram) in normal eyes did not occur in sympathetically denervated eyes. DPAT-induced ocular hypotension was inhibited by pretreatment with spiroxatrine, a 5-HT(1A)and alpha(2C)receptor antagonist, but not spiperone, a 5-HT(2A)receptor antagonist. In contrast, the hypotensive effect produced by unilaterally applied DPAT in the contralateral eye was abolished following pretreatment with rauwolscine, an alpha(2)-receptor antagonist, but the DPAT-induced ocular hypotension was not antagonized in the treated (ipsilateral) eye. Following central administration of DPAT (3 microgram) into the lateral ventricle, intraocular pressure was lowered bilaterally at 10 min and the effect lasted for 2 hr. In in vitro experiments, DPAT (0.1, 1, 10 micrometer) failed to alter norepinephrine release in rabbit iris-ciliary bodies. However, DPAT depressed basal cAMP levels in rabbit iris-ciliary bodies and also caused a dose-related (1, 10, 100 micrometer) inhibition of isoproterenol (1 micrometer)-stimulated cAMP accumulation by 26%, 58% and 82%, respectively. These findings indicate that: (1) based upon bilateral activity by the topical route, DPAT-induced ocular hypotension could result, in part, through activation of 5-HT(1A)receptors in the eye and 5-HT(1A)receptors and/or alpha(2C)adrenoreceptors in the central nervous system, (2) the activity of DPAT on 5-HT(1A)and/or alpha(2C)receptors was confirmed by antagonism of the ocular hypotensive response by spiroxatrine, (3) although there is no apparent prejunctional effect of DPAT on sympathetic nerves of iris-ciliary bodies, the accumulation of basal and isoproterenol-stimulated cAMP levels were depressed by DPAT, and (4) as a result of inhibition by rauwolscine, the ocular hypotensive effect of DPAT in the contralateral eye could involve an action on alpha(2)adrenoreceptors in the central nervous system.     

Effect of topical amosulalol on tissue circulation in the optic nerve head.

The effect of topical 0.1% amosulalol on tissue circulation in the albino rabbit optic nerve head (ONH) was investigated using a laser speckle tissue circulation analyzer. Amosulalol was administered into one eye twice daily for 20 days, and vehicle was administered into the other eye in a masked, randomized manner. Intraocular pressure (IOP) was measured every 5 days. The normalized blur value (NB), a quantitative index of tissue blood flow velocity in the ONH, was measured before treatment and 2 hours after the last instillation on day 20. The IOP was also measured at 5-day intervals. Amosulalol decreased IOP by approximately 2 mmHg in the treated eyes (P < 0.01). There was no significant difference in NB between eyes before the first instillation, whereas NB was significantly greater (by approximately 16%) in the amosulalol-treated eye than in the control eye after completion of instillations (P < 0.01). The difference between NB after completion of instillations and that before the first instillation was significantly greater in the ONH of the amosulalol-treated eye than in the contralateral control eye (P < 0.01). Twice-daily instillation of 0.1% amosulalol for 20 days induced a significant increase in tissue blood velocity in the ipsilateral ONH in albino rabbits.     

Ocular hypotensive effect of alpha-adrenoceptor agonist and antagonist in the conscious pigmented rabbit]

It has been reported that some of the topically-used antiglaucomatics have a central ocular hypotensive effect. In this study, the influence of topical and intracerebroventricular (i.c.v.) administration of phenylephrine, clonidine, guanfacine, prazosin, yohimbine on the intraocular pressure (IOP) was investigated in the rabbit. Male pigmented rabbits were used throughout the experiments. For measurement of IOP, an applanation pneumatonograph was used. By unilateral topical administration of phenylephrine, an increase in IOP in the eye in which instillation was performed was observed. On the other hand, a slight decrease in IOP was observed by similar treatment of prazosin and yohimbine. No significant change of IOP in the contralateral eye was observed with these drugs. On the contrary, unilateral topical administration of clonidine or guanfacine decreased the IOP of both eyes. Furthermore, the decrease of IOP was more remarkable in the contralateral eye compared to the eye which received instillation. The IOP of both eyes was decreased in a dose-related fashion by i.c.v. administration of clonidine or guanfacine. The ocular hypotensive effects of clonidine were diminished by the pretreatment by i.c.v. administration with yohimbine. These results suggest that the ocular hypotensive effect of clonidine and guanfacine is due to their alpha 2-adrenoceptor stimulation in the central nervous system.     

Intraocular pressure effects of timolol after unilateral instillation

Beta-adrenergic antagonists are generally considered to lower intraocular pressure (IOP) of both eyes after unilateral instillation. In order to determine whether timolol also lowers IOP in the contralateral eye and to what extent, pressure curves were established in 14 normal, young subjects. Eye pressure curves on both eyes of each subject were measured before and 1 week after timolol 0.5% instillation twice daily in one eye. All subjects had an IOP decrease in the treated eye, but no subjects had a statistically significant IOP decrease in the contralateral eye. The mean IOP reduction was 26% in the treated eye, and only 3% in the contralateral eye. These results suggest that, in most cases, timolol does not lower IOP in the contralateral eye after unilateral instillation in normal subjects in contrast to certain glaucoma patients. These results suggest two different actions for timolol: (1) a local action in the treated eye, and (2) a systemic action where the pressure-lowering effect in the untreated eye is significant only in some pathologic conditions.     

Effects of topical carteolol and timolol on tissue circulation in the iris and choroid.

PURPOSE: To evaluate the effects of topical carteolol or timolol on tissue circulation in the iris and posterior choroid. METHODS: After a topical instillation of 20 microl of 2% carteolol, 0.5% timolol, or physiological saline (for control) into one eye, and physiological saline into the other eye of pentobarbital-anesthetized Dutch pigmented rabbits, normalized blur value; a quantitative index of tissue blood velocity in the iris (NB(iris)) and posterior choroid (NB(cho)) was obtained using the laser-speckle method. Intraocular pressure (IOP), blood pressure and pulse rate were serially monitored for 2 hours after instillation. Using separate groups of rabbits, NB(iris) and IOP were measured before and after 20-day twice-daily unilateral treatment of carteolol or timolol. RESULTS: After a single instillation of carteolol, NB(iris) was significantly greater only in the treated eyes than control eyes (P = 0.0050, repeated measures two-way ANOVA), while NB(cho) showed no significant change. IOP in the treated eyes significantly reduced (P = 0.0005). Bilateral reductions of tissue vascular resistance in the iris were found after carteolol instillation (P = 0.0183 approximately 0.0322). After timolol instillation, serial changes in NB(iris) and NB(cho) in the treated eyes were significantly different from those in control eyes (P = 0.0129, 0.0031), while there were no significant differences at any of time points (Mann-Whitney test); IOP in both eyes was significantly reduced (P = 0.0096 approximately 0.0005); tissue vascular resistance in the iris and posterior choroid showed no significant changes. After 20-day treatment, NB(iris) in the both eyes of carteolol-treated rabbits significantly increased from the baseline (P = 0.0280, 0.0425, Wilcoxon signed rank test) and NB(iris) in timolol-treated eyes significantly decreased (P = 0.0280). CONCLUSIONS: A single instillation of topical carteolol significantly increased the iris tissue blood velocity in the treated eye and reduced the tissue vascular resistance in both eyes. Topical timolol tended to decrease tissue blood velocity in the iris and choroid of the treated eye, but showed no significant effects on tissue vascular resistance in the both tissues.     

Effect of topical dorzolamide on tissue circulation in the rabbit optic nerve head

PURPOSE: To examine the effect of 1% topical dorzolamide on tissue circulation in the optic nerve head (ONH) of Dutch rabbits. METHODS: A laser speckle tissue circulation analyzer was used. One eye of each rabbit received 1% topical dorzolamide twice daily for 20 days, and the fellow eye received the vehicle in a masked, randomized manner. Intraocular pressure (IOP) was measured every 5 days. The normalized blur (NB) value, a quantitative index of tissue blood flow velocity in the ONH, was measured before treatment and 2 hours after the last instillation on the 20th day. RESULTS: The IOP was lowered by about 2 mm Hg only in the dorzolamide-treated eyes (P < .01). The NB value showed no significant change in either dorzolamide-treated or vehicle-treated eyes. CONCLUSIONS: Long-term topical dorzolamide does not affect the ONH tissue circulation in dorzolamide- and vehicle-treated eyes of Dutch rabbits.     

Biodegradable calcium phosphate nanoparticles as a new vehicle for delivery of a potential ocular hypotensive agent.

The purpose of this study was to determine the efficacy of a newly prepared formulation containing biodegradable calcium phosphate nanoparticles (CAP) and 7-hydroxy-2-dipropyl-aminotetralin (7-OH-DPAT) in pigmented and non-pigmented rabbits using the surrogate end points of intraocular pressure (IOP) and aqueous flow rate. IOP (mmHg) was measured by utilizing a manometrically calibrated Mentor pneumatonometer. Rates of aqueous humor flow were measured with a Fluorotron Master by estimating the dilution rate of fluorescein. In non-pigmented rabbits, the ocular hypotension induced by topical administration of 7-OH-DPAT (75 microg) with CAP (115 microg) was more pronounced and sustained than that of 7-OH-DPAT without CAP. Furthermore, IOP-lowering effects of topically administered 7-OH-DPAT (125 microg) alone were markedly diminished in pigmented rabbits compared to non-pigmented rabbits. However, topical application of 7-OH-DPAT formulated with CAP produced significant dose-related (37.5, 75, 125 microg) reductions of IOP accompanied by suppression of aqueous humor flow rates in pigmented rabbits. It is postulated that 7-OH-DPAT in vehicle without CAP binds to pigments in the anterior segment of the pigmented rabbit's eyes, and this binding limits the 7-OH-DPAT's action. Pretreatment with raclopride, a dopamine D2/D3 receptor antagonist, reduced the ocular hypotensive effect induced by 7-OH-DPAT in vehicle containing CAP thereby supporting the role for dopamine D2/D3 receptors in modulating IOP. It is concluded that CAP, as a delivery system, enhances activity by 7-OH-DPAT in pigmented rabbit eyes suggesting that CAP is potentially useful for achieving controlled and targeted drug delivery for treatment of ocular diseases.     

Effect of topical carteolol on tissue circulation in the optic nerve head

The effect of topical 2% carteolol on tissue circulation in the albino rabbit optic nerve head (ONH) was investigated using a laser speckle tissue circulation analyzer. In the first experiment, the normalized blur (NB) value, a quantitative index of tissue blood flow velocity in the ONH, intraocular pressure (IOP), blood pressure (BP), and pulse rate were measured under general anesthesia before as well as 30, 60, 90, and 120 minutes after a 20-μL instillation of carteolol in one eye and the vehicle in the other eye in a masked, randomized manner. In the second experiment, one eye of a rabbit received carteolol twice daily for 20 days and the fellow eye received the vehicle in a masked, randomized manner. The IOP was measured every 5 days, and the NB in the ONH and IOP were measured before treatment and 2 hours after the last instillation on the 20th day. After a single instillation of carteolol, pulse rate showed a maximum reduction of 15%, and IOP in the carteolol-treated eyes showed a maximum decrease of 22%. The NB in the ONH and BP did not show any significant change during the experiment. After 20-day treatment with carteolol, IOP showed a maximum decrease of 25% in the carteolol-treated eyes and 21% in the vehicle-treated eyes. The NB showed a significant increase of 15% (P < 0.01) in the carteolol-treated eyes and 11% (P < 0.01) in the vehicle-treated eyes. It was indicated that long-term topical carteolol increased the blood velocity in the ONH tissue both in the carteolol- and vehicle-treated contralateral eyes in albino rabbits.     

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 effect of bunazosin hydrochloride on intraocular pressure and aqueous humor dynamics in human]

The effects of bunazosin hydrochloride, a new highly selective alpha 1 adrenergic antagonist, on the intraocular pressure (IOP) and aqueous humor dynamics in healthy human volunteers were studied. Unilateral topical administration of 0.1% bunazosin significantly lowered IOP from 1 to 10 hrs in bunazosin-treated eyes, and from 2 to 8 hrs in contralateral placebo-treated eyes, with its maximum reduction at approximately 3 hrs, when the IOP decreased 5.0 mmHg in treated eyes, and 3.5 mmHg in contralateral eyes from the baseline, respectively. Fluorophotometrically measured aqueous humor flow rates did not change significantly either in treated or contralateral eyes. Bunazosin caused significant reduction of systolic and diastolic blood pressure 5 hr after application. The difference in pupil diameter between treated and contralateral eyes was found to be statistically significant from 1 to 5 hrs. A small but significant increase in anterior chamber depth also was observed from 2 to 6 hrs. Pulse rate and refraction were not substantially altered. There was moderate conjunctival vessel dilation, however, no serious complications were encountered. The results suggest that bunazosin hydrochloride appears to have great clinical potential for ocular hypotensive therapy.     

An acute ocular inflammatory reaction induced by intravitreal bovine serum albumin in presensitized rabbits: the effect of phentolamine

An acute inflammatory reaction in the uvea was challenged by an intravitreal injection of bovine serum albumin (BSA) in presensitized rabbits. During the observation time of 3 h, intraocular pressure (IOP) increased, anterior uveal blood vessels were dilated, miosis was produced, and as a sign of the breakdown of the blood aqueous barrier, protein content in the aqueous humour was increased. In the contralateral eye, the reaction consisted of an increase in IOP and a disruption of the blood aqueous barrier. As an evidence of the immunological mechanism of this acute reaction, presensitized animals intravitreally injected with saline or unimmunized rabbits which were injected with BSA showed no significant changes in IOP, pupillary diameter or protein content in aqueous humour. Phentolamine significantly reduced protein leakage into the anterior chamber of the experimental eye. It also significantly inhibited the increase in IOP and protein leakage in the contralateral eye. The present findings demonstrate that a hypertensive inflammatory phase is present in the acute experimental uveitis. The mechanisms of the reaction and the mode of action of phentolamine are discussed.     

Ocular effects of a N,N-disubstituted 5-OH aminotetralin (N-0437): evidence for a dual mechanism of action

The selective DA2 agonist, N-0437, produced an acute reduction in intraocular pressure (IOP) and pupil diameter (PD) when applied topically to the eyes of normal monkeys. Ocular hypotension and miosis were primarily unilateral in nature, dose-related and lasted 3 to 5 hours following drug instillation. In normal monkeys, 24 to 48 hours following drug administration, a secondary chronic (greater than 24 hrs) reduction in pressure was observed. Once-a-day topical administration of N-0437 (250 micrograms), to normal monkeys, for 4 days produced a chronic unilateral reduction in IOP that persisted for 18 days. Associated with this reduction in pressure on day 2 through 6 were miosis and ptosis of the treated eye. Although topical administration did not lower IOP in rabbits, intracameral injection of N-0437 significantly depressed IOP for 3 days when compared to control injected eyes. Evaluation of ocular sympathetic innervation in N-0437 treated rabbits indicated that these fibers were not functional. In rabbits, intracameral administration of the active (S,-) and inactive (R,+) enantiomer of N-0437 produced equivalent reductions in pressure. These data provide further support for the hypothesis that DA2 receptor agonists can produce acute reductions in IOP. In addition, N-0437 appears to have a second non-receptor mediated mechanism of action that produces a chronic reduction in IOP. This chronic reduction in pressure appears, in part, to result from an interruption of ocular sympathetic nerves function.     

The role of sympathetic cervical ganglion in the effect of clonidine for lowering intraocular pressure]

The contribution of sympathetic cervical ganglion to the mechanism of action of clonidine for lowering intraocular pressure (IOP) was investigated. Pigmented rabbits were used. The animals were divided into 3 groups: normal control group (group 1), animals in which the bilateral cervical sympathetic trunks had been amputated presynaptically (group 2), animals in which the superior cervical ganglion (SCG) had been bilaterally dissected (group 3). Changes in IOP were measured after topical application of clonidine unilaterally. In group 1, IOP was significantly decreased in eye treated by clonidine and contralateral eyes compared to pretreatment values. Decrease of IOP in the contralateral eye was greater than that in the treated eye. In group 2, IOP was decreased in the contralateral eye but increased in the eye treated by clonidine. Pretreatment of yohimbine administered orally antagonized the ocular hypotensive effect of clonidine in a dose-related manner. In group 3, where SCGs were dissected, no changes in IOP were observed in both eyes by unilateral administration of clonidine. These results suggested that the bilateral ocular hypotensive effect of clonidine administered unilaterally is in part due to direct action on the SCG and that the alpha 2 receptor in the SCG plays some role in the regulation of IOP.     

Effects of intracamerally or subconjunctivally injected cross-linked hyaluronic acid on the intraocular pressure and on the anterior segment of the rabbit eye

Cross-linked hyaluronic acid (CLH), a viscoelastic substance with a high viscosity, was injected into the left anterior chamber of 5 rabbits without simultaneous withdrawal of aqueous humour. The right eyes of the same rabbits received an equal amount of sodium hyaluronate (Healon). The intraocular pressure (IOP) of the CLH injected eyes increased four-fold immediately after the injection. One week post injection the IOP had decreased to the pre-injection level where it remained until the euthanatization of the animals 32 days post injection. Biomicroscopically CLH was seen as a slightly opaque curly mass in the anterior chamber in the eyes that otherwise were quiet in four of the rabbits. In one rabbit the injected cross-linked substance reacted immediately with aqueous and turned white. The eye was quiet and showed no inflammatory signs. In all intracamerally injected eyes, slight to moderate aqueous flare was present 4 h post injection. Aqueous flare was still present 1 day post injection in 4 eyes, but was absent 4 days post injection. Histologically no apparent inflammatory reaction was present. Occasional giant cells were seen on the anterior surface of the iris in three animals. Slight accumulation of mononuclear cells was found in the iridocorneal angle of the CLH injected eyes. At histology few mononuclear cells were also found surrounding the subconjunctivally injected CLH still present in 4 additional rabbits when euthanatized 28, 42 and 49 days post injection. The contralateral eye of these 4 animals received an equal amount of sodium hyaluronate subconjunctivally. The substance had been resorbed completely. No reactive or inflammatory signs were present.(ABSTRACT TRUNCATED AT 250 WORDS)