Biomedical subjects

B T Gabelt

Publications and source records attributed to B T Gabelt.

At least 37 records · Page 2Linked to original sources

PubMed1999

H-7 increases trabecular facility and facility after ciliary muscle disinsertion in monkeys.

PURPOSE: To determine the effects of the serine-threonine kinase inhibitor H-7 on total outflow facility in iridectomized + ciliary muscle (CM)- disinserted, and on trabecular facility in normal, monkey eyes. METHODS: Total outflow facility was determined by two-level constant pressure perfusion of the anterior chamber. Trabecular outflow facility was determined from accumulation in blood of intracamerally infused radioiodinated albumin at two intraocular pressure levels. RESULTS: Three-hundred micromoles of intracameral H-7 doubled facility in iridectomized + CM- disinserted monkey eyes and contralateral iridectomized-only eyes. Four 5-microl drops of 400 mM H-7 applied topically followed 2 hours later by anterior chamber exchange for 10 minutes and intracameral infusion for 90 minutes with 100 microM H-7 increased trabecular and total outflow facility by 135%+/-29% and 105%+/-35% (n 5, P < 0.01, P < 0.05), respectively, compared with contralateral vehicle-treated eyes. CONCLUSIONS: H-7 increases trabecular outflow facility in monkeys by a mechanism independent of the CM, presumably acting directly on the trabecular meshwork.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1998

H-7 disrupts the actin cytoskeleton and increases outflow facility.

OBJECTIVES: To determine the effects of the serine-threonine kinase inhibitor H-7 on (1) cell junctions and the attached actin-based cytoskeleton in cultured bovine aortic endothelial cells, and (2) outflow facility in living monkeys. METHODS: Bovine aortic endothelial cells were cultured by standard techniques. The architecture and distribution of actin filaments, vinculin, and beta-catenin in bovine aortic endothelial cells were studied by immunolabeling before and after exposure to H-7 at various concentrations and durations. Outflow facility (perfusion) and intraocular pressure (Goldmann tonometer) were determined before and after the intracameral or topical administration of H-7 or a vehicle. RESULTS: In bovine aortic endothelial cells, exposure to H-7 produced a reversible time- and concentration-dependent disruption of actin microfilaments and an alteration in the organization of cell-cell and cell-matrix adhesions. In monkeys, intracameral and topical administration of H-7 dose dependently and reversibly doubled facility, and topical H-7 reduced intraocular pressures. CONCLUSION: H-7 increases outflow facility in monkeys, probably by inhibiting cell contractility, cytoskeletal support, and cell-cell adhesions in the trabecular meshwork.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1998

Endothelin-1 effects on aqueous humor dynamics in monkeys.

PURPOSE: To report data showing no effect of endothelin-1 on aqueous humor formation and total outflow facility in the cynomolgus monkey, in contrast to the enhancement of outflow facility in monkeys and the suppression of aqueous humor flow in rabbits previously reported by others. METHODS: Living monkeys received, unilaterally: (i) intracameral endothelin-1 (10 microl bolus, or 2ml or 4ml exchange; final intracameral concentration 1 or 10 nM) with total outflow facility measured for up to 1 hr post-treatment by two-level constant pressure perfusion, and (ii) intravitreal endothelin-1 (20 microl, final intravitreal concentration 0.1 or 1 microM) with aqueous humor flow measured by scanning fluorophotometry for 5 hr starting 12 hr post-treatment. Contralateral eyes received vehicle. RESULTS: Endothelin-1 had no effect on total outflow facility or aqueous humor flow with any of the methods described. CONCLUSION: Endothelin-1 seems have a variable effect on aqueous humor dynamics within and between species.

Animals↗

PubMed1997

Atropine reduces but does not eliminate the age-related decline in perfusion outflow facility in monkeys.

Accommodative amplitude and outflow facility decline with age in rhesus monkeys and humans. In monkeys, there is an age-related reduction in ciliary muscle (CM) mobility due to stiffening of its posterior and outer attachments. Since the CM inserts into the trabecular meshwork (TM) and CM contraction deforms the TM so as to increase outflow facility, we asked whether the age-related decline in outflow facility observed in anesthetized monkeys is consequent to the age-related reduction in CM mobility. One eye of 19 pentobarbital-anesthetized rhesus monkeys aged 4-24 years underwent 2-level constant pressure perfusion of the anterior chamber (AC) for 40 min to measure baseline total outflow facility. Both eyes then received 100 micrograms of atropine, given topically to the central cornea. The AC of the second eye was cannulated 40 min after atropine treatment. Facility was measured simultaneously in both eyes for 40 min beginning 45 min after atropine treatment. Baseline facility declined with age by -0.0160 +/- 0.0059 microliters min-1 mmHg-1 yr-1 (P = 0.009). The average facility at baseline was approximately 50% higher in the youngest (ages 4-10 years) compared to the oldest (ages 21-25 years) animals (P < or = 0.03). Following atropine facility decreased by approximately 25% in the youngest monkeys (N.S.), but not at all in the oldest animals when compared to baseline. Thus, the age-related facility decline persisted after atropine in both eyes, but was not as dramatic as prior to atropine (-0.0092 +/- 0.0050 [P < or = 0.09] and -0.0078 +/- 0.0044 [P < or = 0.10] microliter min-1 mmHg-1 yr-1 respectively). Apparently, atropine inhibits facility-relevant anesthetic-induced ciliary muscle tone to a greater extent in younger than in older monkeys, presumably because stiffening of the posterior and outer attachments of the CM in the older animals has already reduced its ability to move and thereby deform the TM. The inability of atropine to completely eliminate the age-related facility decline indicates the presence of atropine-independent, facility-relevant age-dependent changes in the TM itself, such as loss of cells or build-up of extracellular material.

Aging↗

PubMed1997

Effects of adenosine agonists on intraocular pressure and aqueous humor dynamics in cynomolgus monkeys.

The effects of single or multiple topical doses of the relatively selective A1 adenosine receptor agonists (R)-phenylisopropyladenosine (R-PIA) and N6-cyclohexyladenosine (CHA) on intraocular pressure (IOP), aqueous humor flow (AHF) and outflow facility were investigated in ocular normotensive cynomolgus monkeys. IOP and AHF were determined, under ketamine anesthesia, by Goldmann applanation tonometry and fluorophotometry, respectively. Total outflow facility was determined by anterior chamber perfusion under pentobarbital anesthesia. A single unilateral topical application of R-PIA (20-250 micrograms) or CHA (20-500 micrograms) produced ocular hypertension (maximum rise = 4.9 or 3.5 mmHg) within 30 min, followed by ocular hypotension (maximum fall = 2.1 or 3.6 mmHg) from 2-6 hr. The relatively selective adenosine A2 antagonist 3,7-dimethyl-1-propargylxanthine (DMPX, 320 micrograms) inhibited the early hypertension, without influencing the hypotension. Neither 100 micrograms R-PIA nor 500 micrograms CHA clearly altered AHF. Total outflow facility was increased by 71% 3 hr after 100 micrograms R-PIA. In conclusion, the early ocular hypertension produced by topical adenosine agonists in cynomolgus monkeys is associated with the activation of adenosine A2 receptors, while the subsequent hypotension appears to be mediated by adenosine A1 receptors and results primarily from increased outflow facility.

Adenosine↗

PubMed1997

Intraocular pressure and outflow facility are unchanged following acute and chronic intracameral chondroitinase ABC and hyaluronidase in monkeys.

We determined the effect of chronic and acute loss of glycosaminoglycans from the aqueous outflow pathway on intraocular pressure (IOP) and outflow facility in the subhuman primate eye. For the study of the chronic effects of the GAGases, cynomolgus monkeys received intracameral injections of hyaluronidase (Streptomyces, 5 or 50 units, n=2) or chondroitinase ABC (0.05 or 0.25 units, n=2) biweekly for 8 months (4 months for each dose). IOP was measured at 3, 7, 10 and 14 days after each injection. Outflow facility (2-level constant pressure) was determined at 2, 4, 6, and 8 months. Monkeys were killed 6 days after the last injection. The changes in the distribution of hyaluronic acid and sulfated proteoglycans in the outflow pathway were examined using substrate-specific histochemical techniques. The acute effects of these enzymes on outflow facilities (30 min or 2 hr after enzyme) were determined in another group of animals (n=4 for each time enzyme-1). IOP and outflow facility were unchanged compared to controls (heat inactivated enzyme) at any time in the chronically or acutely treated monkeys. Hyaluronic acid staining was absent in the outflow pathways of eyes treated chronically with hyaluronidase compared with control eyes, while collagen-associated sulfated proteoglycans were decreased but not completely removed by the chronic chondroitinase ABC treatment. Chronic loss of these glycosaminoglycans from the trabecular meshwork does not appear to contribute to the IOP elevation and decrease in outflow facility that accompanies open-angle glaucoma. Most importantly, no increase in outflow facility was found with acute hyaluronidase or chondroitinase treatment.

Animals↗

PubMed1997

Effect of DMSO and exchange volume on outflow resistance washout and response to pilocarpine during anterior chamber perfusion in monkeys.

PURPOSE: To determine the dependence of outflow resistance washout on anterior chamber (AC) fluid exchange volume (EV); the minimum EV required for complete AC mixing, and the effect of 0.01-5% DMSO in the exchange solution on outflow resistance. METHODS: Total outflow facility was determined in 63 pentobarbital-anesthetized cynomolgus monkeys, before and after AC exchange, for 10 min, with 1, 2, and 4 ml of Bárány's perfusand, containing 0.01-5% DMSO or containing 1 microgram/ml or 5 micrograms/ml pilocarpine HCL (pilo), each volume. RESULTS: Post-exchange facility increased by 21% (p < 0.05) vs. baseline for both the 1 and 2 ml Bárány's volumes and by 50% (p < 0.001) for the 4-ml volume. Washout-corrected post-exchange facility was unchanged from baseline, following 1 or 2 ml exchange with 1 microgram/ml pilo; 5 micrograms/ml pilo increased facility by 130 +/- 41% and 174 +/- 40% respectively, relative to baseline. Exchange with 4 ml of 1 microgram/ml pilo increased facility 72% more than the 2 ml (p < 0.029) and 100% more than the 1 ml (p < 0.014) volumes. When corrected for their respective baselines, 2 ml of 5 micrograms/ml pilo increased facility 12.7 +/- 4.4% more than the 1 ml volume (p < 0.05). Post exchange facility was not significantly increased over baseline in eyes exchanged with 2 ml of 0.01-4% DMSO or in eyes exchanged with Bárány's alone. When corrected for their respective baselines, post-exchange facility was significantly lower in eyes exchanged with 5% DMSO vs. Bárány's (p = 0.022). CONCLUSIONS: One- and 2-ml EVs preserve outflow resistance equally well, and substantially better than 4 ml. Two ml is the minimum volume necessary for adequate mixing of AC drug solutions, to achieve the full facility effect. Concentrations of DMSO up to 4% in a 2-ml EV can solubilize compounds without additionally decreasing outflow resistance.

Animals↗

PubMed1997

Anterior segment physiology after bumetanide inhibition of Na-K-Cl cotransport.

PURPOSE: To determine the effect of bumetanide inhibition of Na-K-Cl cotransport on aqueous humor formation and outflow facility in living cynomolgus monkeys, outflow facility in organ-cultured human eyes, and contraction in bovine ciliary muscle and trabecular meshwork strips, in vitro. METHODS: Aqueous humor formation in monkeys was measured fluorophotometrically for 6 hours, 1 to 6 weeks before, immediately after, and 2 to 6 weeks after bumetanide was administered intravitreally (final concentration approximately 100 or 500 microM) or intravenously (0.01 or 0.03 mg/ kg at 0 and 3 hours). Outflow facility in monkeys was determined by two-level, constant-pressure perfusion of the anterior chamber for 45 to 60 minutes before and after bumetanide was administered by bolus intracameral injection (100 microM, initial anterior chamber concentration) or by exchanging the anterior chamber with 2 ml 10, 100, or 500 microM bumetanide. Urine volume was measured 3 hours after administration of intravenous bumetanide in various diluents. The effect on intraocular pressure in organ-cultured human eyes was determined for 48 hours by constant-flow-variable-pressure perfusion with 10 microM bumetanide. Contraction of fresh bovine ciliary muscle and trabecular meshwork was measured isometrically with a force-length transducer system after exposure to 100 microM bumetanide +/-1 microM carbachol. RESULTS: The bumetanide concentrations used had little effect on outflow facility or on aqueous humor formation in normal monkeys, on intraocular pressure in organ-cultured human eyes, or on contraction of bovine ciliary muscle and trabecular meshwork strips. Intravenous bumetanide increased urine volume, regardless of the diluent used. CONCLUSIONS: These results suggest that Na-K-Cl cotransport is not involved functionally in regulation of aqueous humor inflow and outflow and in contractility of ciliary muscle and trabecular meshwork.

Aged↗

PubMed1996

Indomethacin and epinephrine effects on outflow facility and cyclic adenosine monophosphate formation in monkeys.

PURPOSE: To investigate the effect of indomethacin inhibition of prostanoid production on the epinephrine-stimulated increase in outflow facility and cyclic adenosine monophosphate (cAMP) production in the anterior segment of the monkey eye. METHODS: Topical indomethacin was given 1 hour before the intracameral administration of epinephrine to living cynomolgus monkeys. Outflow facility was measured for 45 to 60 minutes, beginning 3 hours after epinephrine administration, by two-level constant pressure perfusion of the anterior chamber. Cyclic adenosine monophosphate formation was measured in cell membranes isolated from rhesus monkey ciliary muscle, ciliary processes, trabecular meshwork, and iris in the presence of forskolin, indomethacin, epinephrine, or indomethacin and epinephrine combined. RESULTS: Three hours after the intracameral administration of 5.5 micrograms epinephrine, facility increased by approximately 40%, a putatively maximal response, at which time the intracameral epinephrine concentration was approximately 15 microM. Pretreatment with topical indomethacin produced a dose-dependent inhibition of epinephrine's facility-increasing effect; the maximum inhibition of 50% to 70% occurred at an indomethacin dose of 50 to 125 micrograms. Doubling the indomethacin dose (250 micrograms) produced no further inhibition, whereas a fivefold larger epinephrine dose (27.5 micrograms) did not overcome the inhibition. Forskolin and epinephrine both stimulated cAMP production in vitro, whereas [indomethacin] > or = 10(-4) M partially inhibited both basal and epinephrine-stimulated cAMP production in all four tissues. CONCLUSIONS: Approximately half of the epinephrine-induced facility increase is inhibited by indomethacin, but it is unclear whether the indomethacin-inhibitable fraction is mediated by epinephrine-stimulated prostanoid production or release.

Adrenergic Agonists↗

PubMed1996

Serum effects on aqueous outflow during anterior chamber perfusion in monkeys.

PURPOSE: To prevent the increase in outflow facility during anterior chamber perfusion in nonhuman primates by the addition of autologous serum to Bárány's mock aqueous humor. METHODS: Total outflow facility was measured simultaneously in both eyes of living cynomolgus monkeys for 3 hours by two-level constant pressure perfusion of the anterior chambers from elevated reservoirs with Bárány's solution with (one eye) or without (opposite eye) 3%, 5%, 10%, or 15% to 20% autologous serum. In other experiments, the anterior chamber contents initially were exchanged with Bárány's solution with (one eye) or without (opposite eye) 5% autologous serum, and the facility response to intravenous pilocarpine was determined. RESULTS: Eyes perfused with serum had a lower starting facility than control eyes, with facility decreasing with increasing serum concentrations. For both groups, facility increased with perfusion time and with volume of fluid perfused through the eye, but the rate of change of facility over time and per change in volume was significantly less for the serum-treated eyes. This difference remained significant when the proportional change of facility relative to baseline level was analyzed as a function of time but not as a function of volume. Intravenous infusion of pilocarpine increased facility by approximately the same proportion relative to baseline in both groups, but the absolute change and the final facility were lower in the serum-treated eyes. CONCLUSIONS: Serum or a serum component in the vicinity of the trabecular meshwork normally may help maintain outflow resistance but may be washed away during perfusion with serum-free media.

Animals↗

PubMed1995

Superior cervical ganglionectomy in monkeys: aqueous humor dynamics and their responses to drugs.

The role of sympathetic innervation in regulating the responses of aqueous humor flow, outflow facility and pupillary diameter to timolol and epinephrine was investigated in cynomolgus monkeys following unilateral superior cervical ganglionectomy. Aqueous humor flow was measured fluorophotometrically under pentobarbital anesthesia before the first and after the ninth of twice-daily topical doses of epinephrine, and under ketamine anesthesia before the first and after the ninth of twice-daily topical doses of timolol, 4-19 months after denervation. Baseline aqueous humor flow rates determined 2-4 months following denervation were 40% greater under ketamine than under pentobarbital anesthesia, with no difference between denervated and control eyes. Epinephrine increased aqueous humor flow by up to 50% in a dose-dependent fashion in both eyes, with a non-significant tendency toward slightly greater potency and efficacy in the denervated eyes. Timolol decreased aqueous humor flow by up to 50% in a dose-dependent fashion with equal maximal efficacy in both eyes, but with slightly and statistically significantly greater potency and efficacy in the control eyes at submaximal doses. Early (1-3 months) but not late (23-27 months) after denervation, baseline pupil diameter under ketamine anesthesia was smaller in the denervated eyes than in the controls. The mydriatic response to 600 micrograms epinephrine was more sensitive in the denervated than the control eye both early (1-3 months) and later on (23-27 months) after denervation; timolol had no effect on pupil diameter in either eye. No striking differences in intraocular pressure or refraction were observed between the eyes under any of these conditions. Resting outflow facility or resistance and perfusion-induced facility increase or resistance reduction, measured by two-level constant pressure perfusion under pentobarbital anesthesia 1.5-4.5 years after unilateral sympathectomy, did not differ significantly between sympathectomized and control eyes. Facility increased (by up to 30-50% beyond washout) and resistance decreased (by up to 20-30% beyond washout) similarly in control and sympathectomized eyes 10-60 min and 3-4 hr after bolus intracameral epinephrine doses of 0.55 and 5.5 micrograms.

Animals↗

PubMed1995

Endothelin subtypes: effect on isolated rhesus monkey ciliary muscle.

The effects of endothelin (ET)-1, ET-2, ET-3 and sarafotoxin S6C on the contractile response in the longitudinal and coronal vectors of the isolated rhesus monkey ciliary muscle were studied. Fresh ciliary muscle strips from young and middleaged rhesus monkeys were mounted in an apparatus capable of monitoring contractile force simultaneously in the two vectors. The responses to the ET compounds were measured and compared to those produced with 1 microM carbachol. ET-1 produced contractions of up to 15% of the near-maximum response to carbachol in both vectors of 66% of ciliary muscle strips studied. In responsive strips, the maximal ET-1 induced contraction was approximately equal in both vectors, but the longitudinal vector was approximately 5-fold more sensitive than the circular. All ciliary muscle strips responded reproducibly to carbachol. None of the other ET compounds tested had any effect, suggesting that the ETA receptor may predominate in rhesus monkey ciliary muscle. Because ET-1 induces only weak and interindividually variable contraction in isolated rhesus monkey ciliary muscle strips, ET-1's enhancement of outflow facility with only minimal induction of accommodation in the living monkey may be due to effects directly on the trabecular meshwork. However, the 5-fold greater potency of ET-1 in the longitudinal compared to the circular contractile vector may indicate that selective contraction of the longitudinal portion of the ciliary muscle with consequent deformation of the trabecular meshwork but not the lens is also involved.

Animals↗

PubMed1994

Inhibition of aceclidine-stimulated outflow facility, accommodation and miosis in rhesus monkeys by muscarinic receptor subtype antagonists.

Aceclidine can dissociate accommodative and outflow facility responses in monkeys and humans. We sought to determine if different muscarinic receptor subtypes control outflow facility, accommodative and pupillary responses to aceclidine in the living rhesus monkey eye, as a possible basis for this separation. Each eye was cannulated with one branched and one unbranched needle. Baseline measurements (of outflow facility by two-level constant pressure perfusion; refraction by Hartinger coincidence refractometry and pupil diameter by vernier calipers) were recorded after anterior chamber exchange with (one eye) or without (opposite eye), muscarinic receptor subtype antagonist (pirenzepine, AF-DX 116 or 4-DAMP). The eyes were then exchanged a second time with these solutions plus added aceclidine. The response to aceclidine (the differences from baseline) in the presence or absence of antagonist were compared. The M3 muscarinic receptor subtype antagonist 4-DAMP was the most potent inhibitor of all three responses to aceclidine. The dissociation of accommodative, outflow facility and miotic responses to aceclidine in rhesus monkeys does not appear to be due to differences in the muscarinic receptor subtypes that can currently be distinguished pharmacologically.

Accommodation, Ocular↗

PubMed1994

Apraclonidine and brimonidine effects on anterior ocular and cardiovascular physiology in normal and sympathectomized monkeys.

Apraclonidine and brimonidine administered topically to one eye of ketamine-anesthetized normal cynomolgus monkeys each produced a dose-related bilateral reduction in intraocular pressure which was not dependent on intact sympathetic innervation. Brimonidine was more potent and efficacious (10-12 mmHg maximum intraocular pressure reduction 2 hr after 200 micrograms) but produced a shorter-lasting effect than apraclonidine (4 mmHg maximum intraocular pressure reduction 1-6 hr after 600-1000 micrograms). Apraclonidine had little effect on pupil diameter, but brimonidine produced a dose-related bilateral miosis which was dependent on intact sympathetic innervation. Neither drug significantly affected refractive error. Topical brimonidine, but not apraclonidine, produced a dose-dependent reduction in mean arterial blood pressure, while both drugs lowered heart rate. A dose-dependent bilateral reduction in aqueous humor flow rate calculated over a 6-hr period following drug administration was produced by both topical apraclonidine (maximum 30-35% reduction with 600 micrograms) and brimonidine (maximum 30-45% reduction with 50-250 micrograms), which was not dependent on intact sympathetic innervation. Maintenance of blood pressure by intravenous infusion of angiotensin II had no effect on the aqueous humor flow suppression produced by 100 micrograms of topical brimonidine, but pentobarbital anesthesia abolished it. Intracameral injection of 10 micrograms brimonidine in rhesus monkeys produced an ipsilateral approximately 15% reduction in aqueous humor flow calculated for the 1-3 hr post-injection period. The cardiovascular and contralateral ocular effects observed with both drugs are presumably related to the monkeys' small body weight, and the magnitude of IOP reduction for a given degree of flow suppression would be greater in hypertensive than in normotensive eyes. Caution must therefore be exercised in extrapolating from our data in ocular normotensive monkeys to the glaucomatous human.

Adrenergic alpha-Agonists↗

PubMed1994

The effect of muscarinic agonists and selective receptor subtype antagonists on the contractile response of the isolated rhesus monkey ciliary muscle.

There are ultrastructural and histochemical differences between the longitudinal (putatively more relevant to outflow facility) and circular (putatively more relevant to accommodation) portions of the primate ciliary muscle. Oxotremorine, a muscarinic agonist putatively somewhat selective for the M2 receptor subtype, binds preferentially to the longitudinal rather than the circular portion. Aceclidine, a putatively non-subtype selective muscarinic agonist, can dissociate accommodative and outflow facility responses in monkeys and humans. We used the muscarinic receptor subtype antagonists 4-diphenylacetoxy-N-methylpiperidine methobromide (4-DAMP), 11-([2-(diethylamino)methyl]-1-piperidinyl)acetyl]- 5,11-dihydro-6H-pyrido[2,3b][1,4]benzodiazepine-6-one (AF-DX 116), and pirenzepine to inhibit contractile responses to the muscarinic agonists carbachol, aceclidine and oxotremorine in the longitudinal and circular vectors of the rhesus monkey ciliary muscle in vitro. Oxotremorine generated dose-response curves that were similar in both the circular and longitudinal vectors and intermediate to those previously reported for carbachol and aceclidine. 4-DAMP (M3 selective) was the most potent inhibitor of contractile responses to all three agonists, with IC50 values ranging from 33 to 68 nM for the circular and from 27 to 63 nM for the longitudinal vector, depending on the agonist used to elicit contraction. Pirenzepine (M1 selective) was > or = 25-fold less potent and AF-DX 116 (M2 selective) was > or = 108-fold less potent at inhibiting contractile responses to all three agonists in either vector, indicating that M3 is the predominant receptor subtype mediating ciliary muscle contraction in both vectors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Effect of 8-Br cGMP on aqueous humor dynamics in monkeys.

PURPOSE: To evaluate the effect of 8-bromo cGMP (Br cGMP) on aqueous humor flow rate and outflow facility in monkey eyes. METHODS. Aqueous humor flow rate was measured fluorophotometrically after topical, intracameral, or intravitreal administration of Br cGMP in one eye and normal saline in the other eye. Outflow facility was determined by two-level constant pressure perfusion after intracameral bolus injection of Br cGMP in one eye and Bárány's solution in the other eye. RESULTS: Aqueous humor flow rate decreased by 15% to 20% after intravitreal administration of 10 or 30 micrograms of Br cGMP. There was no flow response to smaller or larger intravitreal doses nor to drugs administered via other routes. Outflow facility increased by 25% to 30% after intracameral infusion of 100 or 300 < gm > g Br cGMP, but not after smaller doses. CONCLUSIONS: cGMP may be involved in the regulation of aqueous humor formation and outflow facility and their responses to pharmacologic agents.

Administration, Topical↗

PubMed1992

Inhibition of outflow facility and accommodative and miotic responses to pilocarpine in rhesus monkeys by muscarinic receptor subtype antagonists.

The muscarinic receptor subtype antagonists 4-diphenylacetoxy-N-methylpiperidine methobromide (4-DAMP), 11-[(2-[diethylamino)methyl]-1- piperidinyl)acetyl]-5,11-dihydro-6H-pyrido[2,3- b][1,4]benzodiazepine-6-one (AF-DX 116) and pirenzepine were used to inhibit the outflow facility and accommodative and miotic responses to near-maximal intracameral doses of pilocarpine in the living rhesus monkey eye. The pharmacologic M3 antagonist 4-DAMP was the most potent inhibitor of all three responses, with IC50 values of 41.7 nM for outflow facility (vs. 40.9 microM pilocarpine), 19.8 nM for accommodation (vs. 40.9 or 81.8 microM pilocarpine) and 3.2 nM for miosis (vs. 4.1 microM pilocarpine). The M1 antagonist pirenzepine was at least 30-fold less potent, with IC50 values of 2.2 microM for outflow facility, 1.4 microM for accommodation and 0.1 microM for miosis. The M2 antagonist AF-DX 116 was the least potent by far, with IC50 values of 15.5 microM for outflow facility, 14.2 microM for accommodation and 1.5 microM for miosis. The results suggest that these three functional responses to pilocarpine are all mediated through an M3 receptor subtype.

Accommodation, Ocular↗

PubMed1991

Outflow facility and its response to pilocarpine decline in aging rhesus monkeys.

Refractive error and total outflow facility were determined by Hartinger coincidence refractometry and two-level constant-pressure perfusion, respectively, in 17 rhesus monkeys, aged 5 to 29 years. Maximum accommodative response to corneal (iontophoretic) carbachol hydrochloride, baseline outflow facility, and the facility response to strong but submaximal intracameral doses of pilocarpine hydrochloride all declined with age. The correlation between accommodative response to carbachol and facility response to pilocarpine was slightly stronger than that between age and facility response. Since the ciliary muscle plays a major role in controlling both outflow facility and accommodation, and since histologic and videographic techniques demonstrate an age-related decline in rhesus ciliary muscle excursion induced by topical pilocarpine or electrical stimulation of the Edinger-Westphal nucleus, the present data support the hypothesis that an age-related decline in ciliary muscle mobility is associated, perhaps causally, with an age-related decline in facility and facility responsiveness to cholinergic drugs.

Accommodation, Ocular↗