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Biomedical subjects

I J Constable

Publications and source records attributed to I J Constable.

At least 127 records · Page 7Linked to original sources
PubMed1991

Effect of rapid alteration in glucose concentration and insulin on thymidine uptake in bovine retinal capillary endothelium.

The effect of insulin and rapid changes in glucose concentration on bovine retinal capillary endothelium (BRCE) was examined by use of tissue culture and 3H-thymidine incorporation. In the absence of insulin, no effect on thymidine uptake by BRCE was observed when glucose concentration was rapidly altered, either increased or decreased. The stimulating effect of insulin on retinal capillary endothelin was more pronounced in log-phase cells than in stationary-phase cells. The extent of stimulation by insulin decreased with increasing glucose concentrations. This effect was not observed when osmotic pressure was increased by mannitol. The results of our experiments make it unlikely that altered osmotic stress, rapidly changing or abnormal glucose levels would be primarily responsible for altered endothelial activity.

Animals↗
PubMed1990

The patency of the retinal vasculature to erythrocytes in retinal vascular disease.

This paper presents the first evidence that in retinas with experimentally induced vascular disease some vessels contain only plasma. This was demonstrated by a histologic technique developed specifically to test the hypothesis that at some stage in retinal vascular disease, vessel patency to erythrocytes is lost before vessels close to plasma. Using this technique, we visualized three major components of the circulation at all retinal locations: the erythrocytes; the plasma as marked by the presence of 0.2-micron fluorescent microspheres; and all functioning endothelial cell nuclei, which were marked by the fluorochrome bis-Benzimide. It was assumed that the distributions of the erythrocytes and small particles in retinal whole mounts reflected accurately the true in vivo distributions at the moment of circulation arrest. Postenucleation the retina can be viewed and photographed within 45 min of circulation arrest. The technique was used on normal rats and on rats induced with a fast-developing model of retinal vasculopathy. With this model, we demonstrated retinal vascular segments perfused by plasma but containing no erythrocytes with functioning endothelial cells in the vessel walls. This may mean that an early factor in some retinal vascular pathologies is tissue hypoxia caused by reduced erythrocyte perfusion.

Alloxan↗
PubMed1990

Laser-induced damage to transparent polymers: chemical effect of short-pulsed (Q-switched) Nd:YAG laser radiation on ophthalmic acrylic biomaterials. I. A review.

The use of short-pulsed lasers in ophthalmic surgery inspired and called for research on the damage inflicted by the laser radiation upon the acrylic polymers from which artificial intraocular lenses are made. The possible release of toxic monomers by laser-induced depolymerization is of great concern but past investigations of this phenomenon have been very limited. The present knowledge of various types of laser-induced damage to transparent polymers is reviewed with particular emphasis on the acrylic materials and intraocular lenses.

Lasers↗
PubMed1990

Laser-induced damage to transparent polymers: chemical effect of short-pulsed (Q-switched) Nd:YAG laser radiation on ophthalmic acrylic biomaterials. II. Study of monomer release from artificial intraocular lenses.

Commercial intraocular lenses and polymer specimens, both poly(methyl methacrylate) (PMMA) and poly(2-hydroxyethyl methacrylate) p(HEMA), were subjected to various levels of irradiation from a Q-switched Nd:YAG laser, and then to extraction and sample-enrichment techniques. The extracts were analysed by capillary gas chromatography. In PMMA samples, residual contents of 0.05-0.89% (wt) MMA were found and it appeared that the laser radiation did not cause a detectable increase of the monomer content. No residual HEMA could be found in p(HEMA) samples before or after laser bombardment. It is concluded that the accidental exposure of lenses to Nd:YAG laser cannot produce a significant release of monomers. Depolymerization induced by laser is a process unlikely to occur at the energy levels used in ophthalmic surgery.

Gas Chromatography-Mass Spectrometry↗
PubMed1990

The effect of glucose and insulin concentration on type IV collagen biosynthesis by bovine retinal capillary endothelial cells in vitro.

Qualitative and quantitative analyses of type IV collagen, newly synthesized by cultured retinal capillary endothelial cells were carried out. After 24-hour incubation in high glucose (25 mM) media with 14C proline there was less type IV collagen synthesis than after incubation in 5.6 mM glucose media. Insulin stimulated the biosynthesis of type IV collagen in both low and high glucose concentrations. The stimulating effect of insulin (on the biosynthesis of type IV collagen) was still observed after inhibition of cell growth with hydroxyurea. High ambient glucose and the insulin effect could play a role in the structural changes observed in diabetic retinal microvascular basement membranes.

Animals↗
PubMed1989

Ridley intraocular lens revisited: chemical analysis of residuals in the original lens material.

Two original Ridley intraocular lenses, made of poly(methyl methacrylate) (PMMA) at least 35 years ago, were extracted in two different media, diethyl ether and water. The extracts were suitably processed and analyzed by high resolution capillary gas chromatography. Residual monomer (MMA) was detected in both extracts. The amount of MMA in the aqueous extract was significantly lower than that in the ether extract. It is postulated that the residual monomer in lenses originated from an incomplete polymerization at the time of the polymer production. However, the MMA content found in one lens (0.147%) is comparable to that currently detected in modern IOLs, and probably does not cause toxic reaction in the eye because it is leached out by aqueous fluid action to a very low extent.

Chromatography, Gas↗
PubMed1989

Chemical investigations of ultraviolet-absorbing hydrogel material for soft intraocular lenses.

A poly(2-hydroxyethyl methacrylate) hydrogel material exhibiting ultraviolet-absorbing properties was synthesized by simultaneous polymerization, crosslinking, and covalent bonding of an available polymerizable absorber. The two-stage leaching experiments carried out by aqueous extraction and the analysis of the concentrated extracts by high resolution capillary gas chromatography showed very low levels of additive released through leaching action. This proves that the ultraviolet absorbers can be successfully incorporated by covalent bonding in soft hydrogel intraocular lenses.

Acrylates↗
PubMed1989

A new method for continuous intraocular drug delivery.

A novel device for the continuous intraocular delivery of drugs is described. The active intraocular component of the device is made from hollow haemodialysis fibres. During operation, the drug to be administered diffuses from a small extraocular reservoir to the intraocular fibres, where it passes through the semipermeable walls and into the vitreous body. The delivery of gentamicin by the device into the vitreous body of the cat is compared with direct intraocular injection techniques. Characteristics of the process of drug delivery were influenced by the geometry and design of the device. A reservoir concentration of 10 g/L gentamicin sulphate in a device with four fibres, each 5 mm long, resulted in stable vitreal gentamicin levels of 104 to 128 mg/L at 10 hours. Intravitreal injection of 0.1 ml of a 10 g/L solution of gentamicin caused localised peaks of intravitreal gentamicin concentration in the range 1180 to 3296 mg/L, before falling to 356 to 665 mg/L at 10 hours. The device provides the opportunity of a more controlled and continuous drug delivery, thus avoiding the high localised concentrations that may occur with direct injection techniques in which the required dose is delivered as a bolus. Refinement of a device of this type may result in a clinically useful method of intraocular drug delivery for drugs which present a risk of localised retinal toxicity or require repetitive administration with conventional intraocular injection techniques.

Animals↗
PubMed1989

Subretinal new vessel recurrence in age-related macular degeneration.

Laser photocoagulation with argon or krypton is currently used to treat selected patients with age-related macular degeneration and sudden visual loss from subretinal new vessel formation. In 102 consecutive cases, treated over two years, closure of the vessels was achieved without additional major visual loss in 79% when assessed at two months. Early failure occurred in 21% and was due either to selection of cases with central location or failure to close the new vessel. Later failures due to recurrent subretinal new vessel formation or progression of other macular degenerative changes has occurred in a further 28% so far. Although controlled clinical trials show a significant benefit of treatment, the overall impact of these few successes on the population with macular degeneration is small. Further understanding of the mechanism of subretinal new vessel formation is urgently required. Areas under investigation include the response of injured retinal pigment epithelium, choroid and retina and cellular production of facilitatory factors including proteases and fibronectin.

Aging↗
PubMed1989

Retinal detachment and its relation to cataract surgery.

In Western Australia during the period 1 January 1976 to 31 December 1987 1089 eyes of 1044 patients in hospital were operated upon for primary rhegmatogenous retinal detachment due to causes other than penetrating trauma. Of these eyes 295 (27%) were aphakic or pseudophakic. During this period the annual number of cataract operations in the State increased by a factor of 245%, while aphakic and pseudophakic retinal detachment operations rose by only 55%. The declining risk of retinal detachment following cataract surgery is attributed to improvements in microsurgical techniques. In 1983 and 1984 the incidence of aphakic and pseudophakic retinal detachments dropped significantly (p less than 0.05). At about this time extracapsular cataract surgery became widespread in the State, and this may explain the observed fall in retinal detachment operations. Since 1984 the incidence has risen owing to the rapidly increasing prevalence of pseudophakia in the resident population.

Adult↗
PubMed1989

Fluorescein angiographic findings in three patients with long-term intravitreal liquid silicone.

The long-term retinal effects of intravitreal liquid silicone (ILS) remain controversial. In this study fundus fluorescein angiographic findings in three patients with long-term ILS are presented. Sluggish or absent blood flow was observed in retinal arterioles that lay in close proximity to the ILS, and the arterioles themselves appeared narrowed. It is suggested that ILS may have a long-term effect on the retinal vasculature, owing either to direct vascular damage, secondary to damage to the neuroretina, or to the ILS preventing diffusion of oxygen into the vitreous cavity.

Adult↗
PubMed1989

Pharmacokinetics of intravitreal injection. Assessment of a gentamicin model by ocular dialysis.

Intravitreal drug administration is the treatment of choice for bacterial endophtalmitis, but improved knowledge of vitreal pharmacokinetics is essential for the development of optimal antibiotic regimes. We used our recently developed sampling device to estimate vitreal gentamicin concentrations for up to 30 hr after an intravitreal bolus injection of gentamicin. The device is based on the principle of dialysis, whereby a constant flow rate of dialysate through a loop of dialysis fiber in the vitreous attains a gentamicin concentration proportional to the intravitreal gentamicin level around the fiber. The dialysate is continuously recovered and the collected samples then assayed for gentamicin. Normal cat eyes and those with induced bacterial endophthalmitis formed the two groups tested. Concentration-time data fitted well to an open single compartment pharmacokinetic model that incorporated the processes of transfer of drug from the injection site to the sampling site (a function of diffusion within the vitreous), and the elimination from the sampling site (a function of elimination from the vitreous). The initial phase of transfer between the injection and sampling site was rapid and rates were comparable in the two groups. Elimination rate constants were uniformly greater in infected eyes than in controls (0.107 hr-1 compared to 0.055 hr-1). Aqueous humor gentamicin concentrations in control eyes varied between 3 and 6 times those found in fellow infected eyes at the end of each experiment. Accelerated elimination of gentamicin from the vitreous body of eyes with endophthalmitis may be explained by increased permeability of the blood-retinal barrier.

Animals↗
PubMed1988

Ocular dialysis. A new technique for in vivo intraocular pharmacokinetic measurements.

A new technique, using the principle of dialysis, enables continuous determination of the concentration of compounds within the vitreous humor of the eye. A semipermeable catheter inserted into the cat vitreous cavity was continuously perfused with a normal saline solution. Gentamicin concentration in the dialysate, after subconjunctival or intravitreal injection, was used to calculate gentamicin concentration in the vitreous from the catheter's recovery ratio, as calibrated in vitro. After subconjunctival injection, no gentamicin was detected in the vitreous for up to eight hours. From four to eight hours after intravitreal injection of approximately 100 micrograms of gentamicin sulfate, its vitreal concentration ranged from 30 to 80 mg/L and from nine to 16 hours it fell from 26 to 22 mg/L. This method may prove useful for the study of the pharmacokinetics of many drugs and metabolites in the eye.

Animals↗
PubMed1988

Retinal detachment following Nd:YAG capsulotomy.

In a retrospective study of 862 patients undergoing Nd:YAG capsulotomy for secondary posterior capsule opacification after extracapsular cataract surgery, the prevalence of retinal detachment was found to be 1.4% with minimum follow-up of six months. Thirty-eight per cent of these detachments occurred within the first two months and 69% occurred within the first six months following capsulotomy. The increase in the prevalence of retinal detachment following Nd:YAG capsulotomy is most likely due to changes in the vitreous which occur when the posterior capsule is no longer intact.

Australia↗
PubMed1988

A new method for oxygen supply to acute ischemic retina.

This paper introduces a new method for supplying oxygen directly to ischemic inner retina, using an oxygen source in the vitreous. Acute retinal vascular occlusion was created in cat eyes by direct pressure on the optic disk and its margins with a glass probe. The satisfactory occlusion of the retinal vessels was documented by direct observation, and functionally by recording the ERG. The vascular occlusion caused a large decrease in the size of the ERG b wave, with no change in the a wave amplitude. The oxygen source was a catheter made of strands of an oxygen-permeable membrane which was inserted into the vitreal cavity. After successful vascular occlusion was documented, 100% gaseous oxygen was perfused through the catheter while recording the ERG. In response to the perfused oxygen the b wave partially recovered. Ventilating the animal with 100% oxygen when the retinal vessels were occluded also caused recovery of the b wave amplitude. Termination of the vitreal oxygen source caused a decrease in b wave amplitude to the level previously observed after the occlusion of the retinal vessels. When the retinal circulation was restored by removal of the glass probe the b wave recovered. The results show that it is possible to supply adequate oxygen to the inner retina via the vitreous to replace the oxygen normally supplied by the retinal circulation. Modification of this method may be useful for the treatment of recent and incomplete retinal vascular occlusion.

Acute Disease↗
PubMed1987

The effect of vitreous humour on prostaglandin production by cultured rabbit chorioretinal fibroblasts.

Factors in vitreous humour which regulate prostaglandin production were investigated using cultured rabbit chorioretinal fibroblasts. These cells produced predominantly prostaglandin E2, 6-ketoprostaglandin F1 alpha, a compound likely to be a metabolite of prostaglandin E2 and 5-hydroxyeicosatetraenoic acid. The synthesis of 6-ketoprostaglandin F1 alpha was nearly completely inhibited by the cyclooxygenase inhibitor aspirin and partially inhibited by 10(-6) M dexamethasone (49%) and 10(-5) M forskolin (68%). Addition of 10% rabbit vitreous humour to subconfluent cells maintained in Dulbecco's modified Eagle's medium plus 1% fetal bovine serum resulted in stimulation of 6-ketoprostaglandin F1 alpha production by as much as 246% as measured by radioimmunoassay. Chorioretinal fibroblasts labelled by [3H]arachidonic acid incorporation into cellular phospholipids synthesised greater amounts of all labelled arachidonic acid metabolites in response to vitreous humour. It was concluded, therefore, that there are factors present in vitreous humour of molecular weight above 10 kDa which are capable of stimulating cellular cyclooxygenase activity. Confluent cells also responded to a factor(s) present in vitreous humour. The fraction of less than 10 kDa inhibited 6-ketoprostaglandin F1 alpha production by 50% when used at a concentration of 10%. Furthermore, 6-ketoprostaglandin F1 alpha production in confluent cells (but not subconfluent cells) was inhibited to 40% of control levels by vitamin C at a concentration of 1 mg/100 ml. The latter result points to an inhibitory role for vitamin C in vitreous humour. We conclude, therefore, that vitreous humour contains factors important for the regulation of prostaglandin metabolism in the eye.

Animals↗