Biomedical subjects

A Bill

Publications and source records attributed to A Bill.

At least 37 records · Page 2Linked to original sources

PubMed1991

Effects of endothelins (ET-1, ET-2 and ET-3) in the rabbit eye; role of prostaglandins.

The effects of intracameral injection of three endothelin isopeptides (ET-1, ET-2 and ET-3) were studied in the rabbit eye. All three peptides at pmol doses caused a dose-dependent rise in intraocular pressure (IOP) and an increase in protein concentration in the aqueous humor, indicating breakdown of the blood-aqueous barrier. Mean arterial blood pressure was not affected. ET-1 was more effective to increase IOP than were ET-2 and ET-3 whose effects seemed to be equal. ET-1 also caused vasodilation in the anterior uvea. The effects of ET-1, ET-2 and ET-3 on the IOP and blood-aqueous barrier, as well as the effects of ET-1 on regional blood flow in the eye, were abolished by pretreatment with indomethacin. Injection of 4 pmol ET-1 into the anterior chamber caused an increase in the concentration of prostaglandin E2 (PGE2) in the aqueous humor, most probably as a result of increased production of PGE2 in the anterior uvea. The results indicate that the effects of ET-1, ET-2 and ET-3 in the rabbit eye are to a large extent mediated by arachidonic acid metabolites.

Animals↗

PubMed1991

Effects of atrial natriuretic factor (ANF) on intraocular pressure and aqueous humor flow in the cynomolgus monkey.

Atrial natriuretic factor (ANF: human sequence) was examined for its effects on basal and terbutaline-stimulated aqueous humor flow, intraocular pressure (IOP) and uveoscleral outflow in cynomolgus monkeys under pentobarbital anesthesia. A dilution method with radioactively labeled albumin was used for the determination of aqueous humor flow. ANF was given by i.v. infusion or intracamerally. Intracameral administration of terbutaline increased the aqueous humor flow significantly; 1.10 +/- 0.05 microliter min-1 in the control eye and 1.69 +/- 0.06 microliter min-1 in the treated eye. I.v. infusion of ANF, 97 fmol kg-1 min-1, increased the aqueous humor flow by about 44% from basal values in the control eye. There was a small but not statistically significant increase on the terbutaline-treated side. The IOP was not changed by ANF at this dose. An ANF dose of 97 pmol kg-1 min-1 increased the aqueous humor flow by 51% in the control eye and by 19% in the terbutaline-treated eye. A further rise of about 8% in aqueous humor flow was registered on the control side when the infused ANF-dose was doubled. Doubling the dose also resulted in a decrease of the IOP by 1.3 +/- 0.3 mmHg on the control side and 2.2 +/- 0.4 mmHg on the terbutaline-stimulated side. Intracameral administration of ANF (81-162 pmol ml-1 perfusion fluid) increased the aqueous humor flow transiently by approximately 50% with a maximum after about 2 hr. The uveoscleral outflow tended to increase and IOP tended to decrease in the ANF-treated eye compared with the control. However, these effects were not statistically significant. These results suggest that ANF may be involved in the control of aqueous humor formation.

Animals↗

PubMed1990

Aspects of oxygen and glucose consumption in the retina: effects of high intraocular pressure and light.

Studies on retinal oxygen and glucose consumption in cats and pigs are reviewed and recent experiments with the deoxyglucose method in monkeys are described. In all three species, the retina is supplied with nutrients by both the retinal and the choroidal blood vessels. Studies on regional blood flow and differences in arteriovenous concentration in cats have indicated that under conditions of general anesthesia and exposure to laboratory light, the oxygen supply from the choroid is about 5.6 microliters/min and that from the retinal vessels, 1.3 microliters/min. In pigs the corresponding figures were about 4 and 2.9 microliters/min, respectively. Moderate reductions in perfusion pressure caused by increments in intraocular pressure or reductions in arterial blood pressure resulted in little change in oxygen tension in the inner retina, due to efficient autoregulation of retinal blood flow. Reduced choroidal blood flow was to a large extent compensated by increased differences in arteriovenous concentration. Studies using the deoxyglucose method in monkeys indicated that pentobarbital anesthesia and constant illumination tend to reduce the metabolism of the retina. In darkness, glucose consumption in the photoreceptors was higher than that recorded under conditions of constant illumination with white light. Flickering light at 4 Hz enhanced glucose consumption in the inner retina. At very high intraocular pressures glucose consumption in the retina was enhanced, probably as a result of partial ischemia, with a shift to more anaerobic glucose metabolism.

Animals↗

PubMed1990

Permeability of ocular vessels and transport across the blood-retinal-barrier.

This paper reviews quantitative studies on the permeability of retinal and choroidal vessels and the exchange of nutrients over the blood retinal barrier (BRB). The fenestrated capillaries in the choroid are very permeable to low molecular weight substances; sodium permeability in the choroid is probably 50 times that in skeletal muscle. This results in high concentrations and rapid turnover of nutrients in the extra-vascular compartment of the choroid. Free diffusion is restricted by the pigment epithelium barrier. Also the retinal capillaries, with tight junctions between the endothelial cells, have very low permeability even to sodium. The uptake index technique has provided evidence for several carrier systems in the BRB; hexoses, neutral and basic amino acids, and monocarboxylic acids, very similar to those found in the brain. At least for glucose and lactate these carriers operate at both levels of the BRB; the RPE and the endothelium of the retinal capillaries, and in both directions; i.e. inwards and outwards.

Animals↗

PubMed1990

Control of retinal and choroidal blood flow.

Earlier studies on the control of retinal and choroidal blood flow are reviewed and some recent observations on the effects of light on retinal metabolism and retinal and choroidal blood flow in monkeys (Macaca fascicularis) are reported in preliminary form. The retina is nourished by the retinal blood vessels, where blood flow is autoregulated and the choroidal blood vessels where autoregulation is absent. Studies with the deoxyglucose method of Sokoloff indicate that flickering light tends to increase the metabolism of the inner retina, while constant light reduces the metabolism in the outer retina. Retinal blood flow in flickering light, 8 Hz, is higher than in constant light. The sympathetic nerves of the choroid are probably involved in a protective mechanism, preventing overperfusion in fight and flight situations with acute increments in blood pressure. The facial nerve contains parasympathetic vasodilator fibres to the choroid; the physiological significance of these fibres is unknown. The neuropeptides NPY, VIP and PHI are likely to be involved in autonomic reflexes in the eye.

Animals↗

PubMed1990

Cholecystokinin causes contraction of the pupillary sphincter in monkeys but not in cats, rabbits, rats and guinea-pigs: antagonism by lorglumide.

The effects of intracameral injections of cholecystokinin (CCK) on the pupil size were determined in monkeys, cats, rabbits, rats and guinea-pigs. In animals under muscarinic cholinergic blockade, CCK caused miosis in monkeys but not in the other species investigated. In monkeys CCK-8 was more potent than CCK-33, which was, however, much more potent than non-sulphated CCK-8. These observations indicate that peripheral type A receptors mediated the miotic response. The effect of CCK-8 was not appreciably influenced by pretreatment with indomethacin, 3 mg kg-1 body wt, indicating that prostaglandins were not involved in the response. Nerve blockade with 0.9 micrograms tetrodotoxin intracamerally had no clear effect on the dose-response relationship for CCK-8. The effect of the peptide thus seems to be directly on receptors on the pupillary sphincter muscle. Pretreatment with lorglumide caused a dose-dependent rightward shift of the dose-response curve, indicating competitive antagonism. The results indicate that in monkeys, but not in rabbit, cats, rats and guinea-pigs, CCK is a potent miotic with a direct effect on the pupillary sphincter mediated by type A CCK receptors on the muscle.

Animals↗

PubMed1990

Effects of timolol on terbutaline- and VIP-stimulated aqueous humor flow in the cynomolgus monkey.

The effects of timolol on terbutaline- and VIP-stimulated aqueous humor flow were investigated in cynomolgus monkeys, with a labeled albumin dilution method. The maximal increase in aqueous humor flow caused by intracameral (100 micrograms/ml) or intravenous (0.4 micrograms/kg/min) administration of terbutaline was about 100%. The effect of intravenously infused terbutaline was completely abolished by intracameral administration of timolol, 0.1 mg/ml. The same dose of timolol also abolished the effect of intravenously infused VIP, 50 ng/kg/min. Intravenous administration of timolol, 0.2 mg/kg, had no effect on VIP-stimulated aqueous humor flow, when VIP (90 micrograms) was given intracamerally, but abolished completely the effect of intracameral terbutaline, 100 micrograms/ml. The results suggest that the effect of intravenously infused VIP on aqueous humor flow is secondary to activation of the sympathetic nervous system, while the effect of intracameral administration of VIP is a direct effect on the ciliary epithelium. The maximal aqueous humor flow achieved with terbutaline is comparable to that in conscious cynomolgus monkeys.

Animals↗

PubMed1989

Increased uveoscleral outflow as a possible mechanism of ocular hypotension caused by prostaglandin F2 alpha-1-isopropylester in the cynomolgus monkey.

The effects of topical application of a single dose of prostaglandin F2 alpha, administered as the isopropylester, on the intraocular pressure (IOP), aqueous humor flow (AHF), conventional, and uveoscleral outflow were studied in cynomolgus monkeys under pentobarbital anesthesia. 1 microgram PGF2 alpha decreased the IOP by 2.9 +/- 0.6 mmHg (3 hr after the application) as compared with the vehicle-treated control eye. The mean AHF during the whole experiment was slightly higher in the experimental than in the control eye, 1.34 +/- 0.11 microliters min-1 compared with 1.16 +/- 0.09 microliters min-1. The uveoscleral outflow was significantly increased in the PGF2 alpha-treated eye, 0.98 +/- 0.12 microliters min-1 compared with 0.61 +/- 0.10 microliters min-1 for the control eye. The conventional outflow was lower in the experimental eye throughout the experiment. Topical application of 10 micrograms pilocarpine at the time when the fall in IOP was expected prevented the drop in the IOP. Simultaneously the increase in the uveoscleral outflow was abolished. After systemic pretreatment with atropine, 1 mg (kg body weight)-1 i.v., there was no significant difference in IOP, AHF, conventional or uveoscleral outflow between the PGF2 alpha-treated, and the control eye. The results of the present investigation suggest that PGF2 alpha decreases the intraocular pressure by increasing the uveoscleral outflow. The mechanism behind the increase in the uveoscleral outflow remains to be established. Relaxation of the ciliary muscle as well as enlarged intramuscular spaces and loss of extracellular material may contribute to the effect.

Animals↗

PubMed1989

The pressures in the episcleral veins, Schlemm's canal and the trabecular meshwork in monkeys: effects of changes in intraocular pressure.

The pressures in the episcleral veins, Schlemm's canal and the trabecular meshwork were studied with a micropuncture technique using cannulas with tip diameters of less than 5 microns. The pressure in Schlemm's canal, Psc, was 14.3 +/- 1.0 cmH2O at spontaneous intraocular pressure, IOP, 19.2 +/- 0.9 cmH2O. The outflow pressure from the anterior chamber to Schlemm's canal was 4.9 +/- 0.7 cmH2O. The relationship between pressures was IOP = 0.73 Psc + 8.7. When the intraocular pressure was increased stepwise from the spontaneous level to 30 cmH2O there was an increase in pressure in Schlemm's canal of 1.7 +/- 0.6 cmH2O, (P less than 0.05). The total outflow resistance and the resistance between the anterior chamber and Schlemm's canal were 3.27 +/- 0.43 and 2.92 +/- 0.50 cmH2O min microliter-1 respectively for the intraocular pressure interval between the spontaneous pressure and a level 4-11 cmH2O higher. In the intraocular pressure range from 20 to 30 cmH2O the corresponding figures were 2.89 +/- 0.45 and 2.69 +/- 0.42 cmH2O min microliter-1 and for the pressure range 25-35 cmH2O, 2.48 +/- 0.58 and 2.31 +/- 0.59 cmH2O min microliter-1. The difference between the total outflow resistance and that between the anterior chamber and Schlemm's canal was about 10% of the total at intraocular pressures below 35 cmH2O. Stepwise increments in IOP increased the trabecular meshwork pressure by 0.88 cmH2O for each cmH2O increase in IOP in the interval of 30-50 cmH2O. The total outflow resistance and the resistance between the anterior chamber and the tip of the microcannula was 3.91 +/- 1.53 and 1.94 +/- 0.99 cmH2O min microliter-1 respectively for the intraocular pressure interval between the spontaneous pressure and 30 cmH2O. In the interval between 30 and 45 cmH2O the corresponding figures were 2.16 +/- 0.66 and 0.20 +/- 0.13 cmH2O min microliter-1. The episcleral venous pressure at the spontaneous intraocular pressure was 14.1 +/- 1.0 cmH2O in seven animals with minimal trauma, and 12.3 +/- 0.8 cmH2O in animals after cannulation of Schlemm's canal. The outflow pressure from the anterior chamber to the episcleral veins was 4.4 +/- 1.2 cmH2O in animals with minimal trauma and 7.1 +/- 0.8 cmH2O after cannulation of Schlemm's canal. The relationship between pressures was IOP = 0.68EVP + 11.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1989

[Aspects of aqueous humor drainage through Schlemm's canal].

The structure and function of the outflow routes via Schlemm's Canal are discussed. Recent measurements of the pressure in the intertrabecular space, Schlemm's canal, and the episcleral veins in monkeys indicate that most of the resistance is located between the anterior chamber and Schlemm's canal. Platelets may play a role in Schlemm's canal by occluding artificial breaks and pores which are large enough to permit contact between platelets and the subendothelial tissue. The invaginations of the endothelial cells of the inner wall of Schlemm's canal are likely to prevent such contact if the pores in their wall towards the canal are small.

Animals↗

PubMed1989

Effects of intravenous calcitonin gene-related peptide (CGRP) and substance P on the blood-aqueous barrier in the rabbit.

The irritation response of the rabbit eye to trigeminal nerve stimulation, which includes a breakdown of the blood-aqueous barrier (BAB), seems to be due to the release of substance P (SP) and calcitonin gene-related peptide (CGRP). In order to assess the relative importance of these two peptides for the barrier effect, and the role of arachidonic acid metabolites (AAM) in the response, we have studied the effects of intravenous injections of the peptides on the permeability of the blood vessels of the anterior uvea and the BAB using labelled albumins. At a dose of 120 pmol kg-1 there was marked leakage of labelled albumin into the aqueous humour in animals under pentobarbital anaesthesia. The leakage was enhanced by sympathotomy. In conscious animals 5 pmol kg-1 CGRP caused enhanced leakage from the blood vessels of the ciliary processes in those pre-treated with biperiden in order to abolish the cholinergic vasoconstrictor tone in the anterior uvea. 24 and 120 pmol kg-1 CGRP caused marked leakage of albumin and a breakdown of the epithelial part of the BAB. These effects were not modified by biperiden pre-treatment, but markedly reduced by pre-treatment with indomethacin. The protecting effect of indomethacin was lost when biperiden was given as well. SP did not cause a leakage with 5 nmol kg-1 and only moderate leakage with 25 nmol kg-1. This effect was abolished by pre-treatment with indomethacin but not if indomethacin was combined with biperiden.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Uveoscleral drainage of aqueous humor: physiology and pharmacology.

Uveoscleral outflow can account for 35% to 60% of total outflow in monkeys, although only for a much lesser fraction in cats and rabbits. Accurate assessment of the percentage of outflow via this route in humans is more difficult. In human eyes, this value was found to be in the 5% to 25% range by isotope studies, although calculations based on non-invasive methods have suggested a value of about 35% in normal eyes. In monkey eyes, the rate of uveoscleral outflow is not much affected by IOP but it can be increased by surgical and pharmacological means. Epinephrine, for example, has been found to increase uveoscleral outflow, possibly mediated by endogenously synthesized PGs. In monkeys, observed increases in uveoscleral outflow following administration of very small PG doses equal or exceed the increase that can be achieved with much higher doses of epinephrine. These observations support the concept that PGs may represent an important new approach to the medical management of glaucoma.

Animals↗

PubMed1989

The effect of prostaglandin F2 alpha-1-isopropylester (PGF2 alpha-IE) on uveoscleral outflow.

These studies assessed the acute effects of a single dose of prostaglandin F2 alpha-1-isopropylester (PGF2 alpha-IE) on the IOP and AHF, as well as on conventional and uveoscleral outflow, in cynomolgus monkeys. The AHF was determined by a dilution method, using radioactive albumin as a marker. Arterial blood samples were collected and analyzed for radioactivity to determine the flow of aqueous humor to blood, corresponding to the conventional outflow. The uveoscleral outflow was calculated as the difference between the measured AHF and the conventional outflow. Topical application of PGF2 alpha-IE (1 microgram free acid equivalents) to eyes of cynomolgus monkeys caused a small initial increase in IOP followed by a gradual decrease, which was greatest (2.9 +/- 0.6 mmHg below the control eye) at about three hours after the PG application. The mean AHF during 4 hours was slightly higher in the experimental eyes than in the control eyes. The mean uveoscleral outflow during 4 hours was significantly higher in the experimental eyes (0.98 +/- 0.12 microliters.min-1) than in the control eyes (0.61 +/- 0.10 microliters.min-1), while the conventional outflow was significantly lower. The ability of PGF2 alpha-IE to increase the uveoscleral outflow was also demonstrated by autoradiography. These results suggest that PGs exert at least part of their ocular hypotensive effect by increasing the uveoscleral outflow. It remains to be established whether this effect is caused by relaxation of the ciliary muscle or whether other mechanisms, such as structural and metabolic changes, are involved.

Administration, Topical↗

PubMed1988

Effects of alpha-chymotrypsin on the outflow routes for aqueous humor.

The anterior chamber was perfused with alpha-chymotrypsin, 50 micrograms ml-1, in mock aqueous humor in cynomolgus monkeys. The enzyme caused a marked rise in outflow facility and had clear effects on the structure of the outflow routes for aqueous humor. The intertrabecular spaces in the iridocorneal chamber angle were wider than normal, the openings in the uveal and corneoscleral meshwork appeared enlarged, there was ballooning of the juxtacanalicular region and the inner wall of Schlemm's canal into the canal and also splitting of the inner wall of the canal. The trabecular cells appeared relaxed with most of the cell processes retracted, some broken. There were discontinuities in the cell membrane and blebs. Parts of the trabecular beams were denuded. Two days after the enzyme treatment the facility was in the normal range, no splits in the inner wall of Schlemm's canal we observed but many of the other changes in structure remained. The number of invaginations in the inner wall of Schlemm's canal was markedly reduced after 2-18 days. A second and third perfusion with alpha-chymotrypsin caused a rise in outflow facility similar to the first. Some morphological changes remained 163 days after enzyme treatment. Pilocarpine a few days after alpha-chymotrypsin treatment caused a marked increase in outflow facility. The results suggest that alpha-chymotrypsin affects the glycoproteins of the cell membrane and as a result causes disorganization of the cytoskeleton, loss of loose adhesions and breaks of cell processes. The rapid recovery of the resistance to outflow was probably due to healing of the splits in the inner wall of Schlemm's canal; a marked reduction in the number of cells with invaginations suggests that in addition there may have been a reduction in the number of transcellular pores in the inner wall of Schlemm's canal.

Animals↗

PubMed1987

Morphological and functional effects of Na2EDTA on the outflow routes for aqueous humor in monkeys.

The chelating agent Na2EDTA was perfused through the anterior chambers of monkeys eyes in an attempt to find a concentration that would cause a rise in outflow facility without harming the cornea or anterior uvea. Na2EDTA (0.5 mM) proved effective in increasing the facility within 60 min. There were marked effects on the tissue at the iridocorneal chamber angle with loss of cell processes from the trabecular cells, ballooning of the juxtacanalicular region and the inner wall of Schlemm's canal into the canal and ruptures of the inner wall of Schlemm's canal. After 60 min of perfusion there were mild vascular changes in the ciliary muscle and the iris and more pronounced stasis and leukocyte extravasation at the base of the ciliary processes and in the pars plana region. The corneal endothelium tended to swell but only after prolonged perfusion. After interruption of the perfusion there was rapid reduction in outflow facility, that seemed to be due to occlusion of the ruptures in Schlemm's canal by thrombocytes.

Animals↗

PubMed1987

The microsphere method for measuring low blood flows: theory and computer simulations applied to findings in the rat cochlea.

When the microsphere method of blood flow measurement is used in small organs, the number of spheres actually recovered may be small. This introduces errors which, however, are not necessarily important as compared with the biological variation. A mathematical model was constructed which allowed estimation of the extra uncertainty caused by the low number of spheres. It was applied to an experimental material of over 100 measurements of cochlear blood flow in the rat, where only about 60 spheres were recovered per cochlea. It was concluded that this paucity of spheres introduced only a small to moderate extra error. Simple approximate formulae were derived allowing easy estimation of the uncertainty caused by low number of spheres under different conditions. In general, there appear to be many situations where fewer microspheres than are commonly used would suffice.

Age Factors↗

PubMed1986

Effects of vasoactive intestinal polypeptide (VIP) on intraocular pressure, facility of outflow and formation of aqueous humor in the monkey.

Stimulation of the facial nerve causes a non-cholinergic vasodilation in the uvea and a rise in the intraocular pressure in rabbits, cats and monkeys. Vasoactive intestinal polypeptide (VIP) has been suggested as the neurotransmitter mediating these effects. In the present investigation, the effects of VIP on aqueous humor dynamics were studied in cynomolgus monkeys. After intracameral injection of 1 microgram VIP, the outflow facility was higher in the experimental eye than in the control; 0.42 +/- 0.46 compared with 0.33 +/- 0.03 microliter cm H20-1 min-1, difference 0.09 +/- 0.04 microliter cm H2O-1 min-1. Intravenous infusion of VIP, 160 ng min-1, increased aqueous humor flow from 1.12 +/- 0.07 to 1.65 +/- 0.09 microliter min-1. Almost the same effect, a 50% increase in aqueous humor flow, was found after intracameral administration of 90 micrograms VIP. This dose of VIP caused a significant increase in intraocular pressure (IOP) in the experimental eye. The maximal difference in IOP between the experimental eye and the control eye was 7.5 +/- 0.4 cm H2O. A lower dose of VIP, 30 micrograms intracamerally, increased aqueous humor flow by about 20%, but had no consistent effect on IOP. The effect of VIP on aqueous humor flow was not affected by pretreatment with indomethacin. The results suggest that most of the rise in IOP caused by intracameral VIP administration is due to a rise in the pressure in the veins into which the aqueous humor is drained. Enhanced formation of aqueous humor plays a smaller role. The effects of VIP on aqueous humor formation and outflow facility suggest that the facial nerve may be involved in nervous control of aqueous humor dynamics, as VIP is most probably released in the eye by stimulation of the facial nerve.

Animals↗

PubMed1986

Effects of B-HT 920 in the eye and on regional blood flows in anaesthetized and conscious rabbits.

The influence of unilateral ocular instillation of B-HT 920 (50 micrograms) on regional ocular, cerebral and peripheral blood flows was investigated with the labelled microsphere method in conscious and anaesthetized albino rabbits. In urethane-anaesthetized rabbits the intraocular pressure (IOP) fell during 1 hr following topical B-HT 920 whereas no changes in regional blood flows were observed. Only in conscious rabbits was a decrease in regional blood flows found. B-HT 920 caused a short-term reduction in choroidal blood flow by about 20%. Transient vasoconstrictor effects, due to systemic absorption, were also seen in some extraocular tissues. Concomitantly, B-HT 920 reduced the total cerebral blood flow (CBF) by 23%. In the grey matter and hypothalamic region the decrease in flow was about 20%, while in the hippocampal region, thalamic region, collicles and pons-mesencephalon it was about 10%. In experiments with direct blood flow determination from an opened vortex vein, there was no consistent change of uveal vascular resistance, while IOP and mean arterial pressure (MAP) fell dose-dependently following cumulative intravenously administered bolus doses (10 and 50 micrograms/kg) of B-HT 920. Unilateral loss of the mediated sympathetic tone seemed to increase the ocular responses to B-HT 920, unmasking a vasoconstrictor effect. Additional systemic pretreatment with the selective blocking agents rauwolscine and sulpiride suggests that B-HT 920 produces its ocular hypotensive effect, predominantly by acting on dopamine (DA2) receptors in the eye rather than on alpha 2-adrenoceptors, and its ocular vasoconstrictor effects via both receptor types.

Anesthesia↗