Biomedical subjects

S J Cringle

Publications and source records attributed to S J Cringle.

At least 19 recordsLinked to original sources

PubMed2005

Confocal laser Doppler flowmeter measurements in a controlled flow environment in an isolated perfused eye.

The aim of this study was to improve our ability to interpret and validate Heidelberg Retina Flowmeter (HRF) flow images by recording flow measurements from specific regions of the retinal vasculature by taking advantage of the ability to precisely regulate perfusion flow in an isolated eye preparation. The retinal vasculature in 16 isolated perfused pig eyes was perfused with a 50%/50% Krebs/RBC solution at known flow rates ranging from 0 to 300 microl min(-1). At each flow rate, HRF images were obtained at a location approximately two disc diameters from the disc. After HRF image acquisition, the retinal vasculature was perfused with fluorescein isothiocyanate for fluorescence microscopy. Using the standard HRF software and a 10 x 10pixel measurement window, flow rates were measured from a retinal artery, vein, arteriole, venule, and the retinal capillary bed and a capillary-free-zone. The relationship between HRF measured flow and perfusion flow in the different measurement locations was determined. At zero perfusion flow the measured HRF flow was consistently greater than zero ( approximately 170 arbitrary units (AU)), and not significantly different at each measurement location except for the retinal vein, which had a significantly higher HRF flow value ( approximately 230AU). At higher perfusion flow rates the flow signal from the larger vascular elements (arteries and veins) increased rapidly thereafter to reach several thousand AU at a total perfusate flow of 50 microlmin(-1) and increased less rapidly at higher flow rates. In arterioles, the HRF flow was more linear over a broader range of perfusate flow rates but the peak flow signal was an order of magnitude smaller than that from the retinal artery. Both the linearity and magnitude of the flow signal in venules was less than that in arterioles. In capillary areas and in the capillary free zone, the HRF flow showed only a very weak relationship to perfusion flow when compared to the background noise. The choice of location for HRF flow analysis greatly influences the ability of the technique to measure changes in retinal blood flow. The major arteries and veins provide the strongest signal and greatest signal to noise ratio. However, the retinal arterioles produce an HRF signal that is more linear over a wider range of perfusate flow rates.

Animals↗

PubMed2002

Agonist-induced vasoactive responses in isolated perfused porcine dental pulpal arterioles.

A novel isolated perfused pulpal arteriole preparation and microperfusion system was used to evaluate the direct vasoactive responses of pulpal arterioles to selected agonists. Short lengths of porcine pulpal arterioles (101.7+/-2.2 microm o.d., n=105) were dissected out and placed in an environment-controlled bath on the stage of an inverted microscope. Both ends of the vessel were cannulated and perfused at a controlled rate through the lumen. The diameter of the vessel was measured online. Following equilibration, the vessel was challenged with various agonists: adrenaline (epinephrine), noradrenaline (norepinephrine), phenylephrine, dopamine, isoproterenol, 5-hydroxytryptamine, histamine and adenosine. The endothelium-dependent vasodilator acetylcholine was used to evaluate endothelial cell function. Adrenaline, noradrenaline, phenylephrine, 5-hydroxytryptamine and dopamine caused dose-dependent contractions (adrenaline=noradrenaline>phenylephrine>dopamine>5-hydroxytryptamine). Isoproterenol and histamine provoked a dose-dependent dilation. Adenosine produced pronounced vasodilatation in vessels precontracted with 10(-8)M endothelin-1. Functional adrenergic, histamine, 5-hydroxytryptamine and adenosine receptors are, therefore, present in porcine pulpal arterioles. The isolated perfused pulpal arteriole preparation may prove valuable in understanding local control mechanisms of pulpal microcirculation.

Adenosine↗

PubMed2002

Oxygen distribution and consumption in rat lower incisor pulp.

The aim was to determine the oxygen tension (P(O(2))) and rate of oxygen consumption in the pulp. Twelve rats were anaesthetised and artificially ventilated. Under an operating microscope, a recessed oxygen-sensitive microelectrode was inserted into the pulp through a small saline-covered cavity on the labial surface of the lower incisor. P(O(2)) was measured as a function of the transverse distance from the saline medium through to the middle of the pulp. Oxygen profiles were characterised by a decline of oxygen tension outside the pulp in the saline medium and a steeper gradient across the interface, before a localised oxygen consuming region corresponding to the odontoblasts. A plateau with some localised fluctuations was then followed by an increase in oxygen tension in the middle of the pulp. The average oxygen tension in the plateau region was 23.2 mmHg+/-2.1 mmHg (n=12). A mathematical model was used to extract oxygen consumption data from P(O(2)) profiles recorded from non-perfused pulp (created by reducing systemic blood pressure). The analysis revealed that there was a distinct oxygen consumption zone in the outer pulp, which anatomically corresponded to the odontoblast layer. The average oxygen consumption rate of the odontoblasts was 3.2+/-0.2 ml O(2)/min per 100g pulp tissue. The zone of high oxygen consumption was 68.7 micro m+/-6.9 micro m (n=24) thick. It is concluded that pulpal oxygen distribution is heterogeneous and that the odontoblast could be a major oxygen consumer within the rat incisor pulp.

Animals↗

PubMed2002

An in vivo and in vitro comparison of the effects of vasoactive mediators on pulpal blood vessels in rat incisors.

The effects of endogenous vasoactive substances were evaluated in anaesthetized rats using a laser Doppler flowmeter to monitor changes in pulpal blood flow, as well as directly in isolated pulpal arteriole preparations utilising a microperfusion and monitoring system to observe changes in vessel diameter. In anaesthetized rats, while systemic arterial blood pressure remained relatively stable, intra-arterial delivery of adrenaline (epinephrine) (A), noradrenaline (norepinephrine) (NA), phenylephrine (PHE), dopamine (DOPA), 5-hydroxytryptamine (5-HT), or endothelin-1 (ET-1) produced a dose-dependent reduction in pulpal blood flow (order of potency: ET-1>>A=NA>PHE=DOPA=5-HT); acetylcholine induced a dose-dependent increase in pulpal blood flow; histamine, isoproterenol and adenosine produced no significant changes. In isolated arteriole preparations, intraluminal delivery of A, NA, PHE, DOPA or 5-HT produced dose-dependent vasoconstriction (A=NA>PHE=DOPA=5-HT). Acetylcholine relaxed NA-precontracted vessels dose-dependently. Histamine and isoproterenol produced a small vasodilatation. Intraluminal ET-1 produced a small vasoconstriction at 10(-8)M, whereas extraluminal ET-1 produced a dose-dependent vasoconstriction from 10(-10)M and above. Intraluminal adenosine failed to dilate vessels precontracted with ET-1, whereas extraluminal adenosine caused a complete relaxation. These combined in vivo and in vitro data suggest that, in the rat incisor, the pulpal microcirculation is capable of functional regulation and that pulpal blood flow may be modulated by endothelium-related factors, metabolic (tissue-related) factors, as well as humoral (blood-borne) factors.

Analysis of Variance↗

PubMed2001

Oxygen distribution and consumption within the retina in vascularised and avascular retinas and in animal models of retinal disease.

Maintenance of an adequate oxygen supply to the retina is critical for retinal function. In species with vascularised retinas, such as man, oxygen is delivered to the retina via a combination of the choroidal vascular bed, which lies immediately behind the retina, and the retinal vasculature, which lies within the inner retina. The high-oxygen demands of the retina, and the relatively sparse nature of the retinal vasculature, are thought to contribute to the particular vulnerability of the retina to vascular disease. A large proportion of retinal blindness is associated with diseases having a vascular component, and disrupted oxygen supply to the retina is likely to be a critical factor. Much attention has therefore been directed at determining the intraretinal oxygen environment in healthy and diseased eyes. Measurements of oxygen levels within the retina have largely been restricted to animal studies in which oxygen sensitive microelectrodes can be used to obtain high-resolution measurements of oxygen tension as a function of retinal depth. Such measurements can immediately identify which retinal layers are supplied with oxygen from the different vascular elements. Additionally, in the outer retinal layers, which do not have any intrinsic oxygen sources, the oxygen distribution can be analysed mathematically to quantify the oxygen consumption rate of specific retinal layers. This has revealed a remarkable heterogeneity of oxygen requirements of different components of the outer retina, with the inner segments of the photoreceptors being the dominant oxygen consumers. Since the presence of the retinal vasculature precludes such a simple quantitative analysis of local oxygen consumption within the inner retina, our understanding of the oxygen needs of the inner retinal components is much less complete. Although several lines of evidence suggest that in the more commonly studied species such as cat, pig, and rat, the oxygen demands of the inner retina as a whole is broadly comparable to that of the outer retina, exactly which cell layers within the inner retina have the most stringent oxygen demands is not known. This may be a critical issue if the cell types most at risk from disrupted oxygen supply are to be identified. This paper reviews our current understanding of the oxygen requirements of the inner and outer retina and presents new data and mathematical models which identify three dominant oxygen-consuming layers in the rat retina. These are the inner segments of the photoreceptors, the outer plexiform layer, and the deeper region of the inner plexiform layer. We also address the intriguing question of how the oxygen requirements of the inner retina are met in those species which naturally have a poorly vascularised, or even totally avascular retina. We present measurements of the intraretinal oxygen distribution in two species of laboratory animal possessing such retinas, the rabbit and the guinea pig. The rabbit has a predominantly avascular retina, with only a narrow band of retinal vasculature, and the guinea pig retina is completely avascular. Both these animals demonstrate species adaptations in which the oxygen requirement of their inner retinas are extremely low when compared to that of their outer retinas. This finding both uncovers a remarkable ability of the inner retina in avascular species to function in a low-oxygen environment, and also highlights the dangers of extrapolating findings from avascular retinas to infer metabolic requirements of vascularised retinas. Different species also demonstrate a marked diversity in the manner in which intraretinal oxygen distribution is influenced by increases in systemic oxygen level. In the vascularised rat retina, the inner retinal oxygen increase is muted by a combination of increased oxygen consumption and a reduction of net oxygen delivery from the retinal circulation. The avascular retina of the guinea pig demonstrated a novel and powerful regulatory mechanism that prevents any dramatic rise in choroidal oxygen levels and keeps retinal oxygen levels within the normal physiological range. In contrast, in the avascular regions of the rabbit retina the choroidal oxygen level passively follows the increase in systemic oxygenation, and there is a dramatic rise in oxygen level in all retinal layers. The presence or absence of oxygen-regulating mechanisms may well reflect important survival strategies for the retina which are not yet understood. Intraretinal oxygen measurements in rat models of retinal disease are also presented. We describe how oxygen distribution across the rat retina is influenced by manipulation of systemic blood pressure. We examine the effect of acute and chronic occlusion of the retinal vasculature, and explore the feasibility of meeting the oxygen needs of the ischemic retina from the choroid. (ABSTRACT TRUNCATED)

Animals↗

PubMed2001

Pathogenesis and intervention strategies in diabetic retinopathy.

Diabetic retinopathy is the leading cause of new blindness in the working-age population. If improved treatment regimens are to be developed it is crucial that the underlying pathophysiological mechanisms responsible for diabetic retinopathy are better understood. The multifactorial nature of the many pathways implicated in diabetic retinopathy requires a very detailed approach to elucidate the key mechanisms involved and their interactions in order to develop logical strategies aimed at therapeutic intervention. Fortunately, the streptozotocin rat model of diabetes displays many of the morphological and functional changes to the retinal vasculature that are evident in human diabetic retinopathy. This study reviews some of the recent experimental work by the authors in the streptozotocin rat, compares their findings to the human pathology and outlines potential new avenues for therapeutic intervention. In particular the improved understanding of which layers of the inner retina have the most stringent metabolic demands has helped identify which retinal layers are most susceptible to metabolic or hypoxic/ischaemic insult. It is concluded that improved treatment outcomes may ensue if the therapy is targeted at the appropriate tissue at specific stages of the disease.

Animals↗

PubMed2001

Tetrahydrobiopterin reverses the impairment of acetylcholine-induced vasodilatation in diabetic ocular microvasculature.

The purpose of this study is to test whether tetrahydrobiopterin, an essential cofactor in nitric oxide synthesis, can reverse endothelium dysfunction in diabetic ocular circulation. Using the streptozotocin-induced diabetic rat model and the isolated perfusion eye technique, the response to the acetylcholine (an endothelium-dependent vasodilator mediated by stimulated nitric oxide release) induced vasodilatation of the diabetic ocular vasculature before and after tetrahydrobiopterin administration was compared. Age matched normal rats were used for reference response. Six streptozotocin-induced diabetic rats and eleven control rats at 21.5 +/- 0.2 weeks and 21.2 +/- 2.1 weeks postinduction, respectively, were used. The dose response curve from the diabetic eyes was found to be significantly different from that of the control eyes (p < 0.001) with significantly reduced responses to 10(-4)M acetylcholine. After 30 min of administration of tetrahydrobiopterin to the diabetic eyes, however, the acetylcholine-induced vasodilatation response was significantly (p < 0.001) increased compared with the response prior to tetrahydrobiopterin administration. The vasodilatory response in the diabetic eyes after tetrahydrobiopterin administration was at a level that was comparable with the control response (p = 0.742). We have shown that acute administration of tetrahydrobiopterin is effective in reversing to control level the impaired acetylcholine-induced vasodilatory response at 21.5 +/- 0.2 weeks postinduction. Our result suggests that a decreased level of tetrahydrobiopterin in the eyes of the streptozotocin-induced diabetic rats may be responsible for the ocular vascular endothelium dysfunction.

Acetylcholine↗

PubMed2001

Acetylcholine-induced vasodilation of isolated pulpal arterioles.

The presence of cholinergic mechanisms in the control of pulpal microcirculation has been a controversial issue. In this study, we aimed to determine the direct vasoactive responses of isolated pulpal arterioles to acetylcholine, and to investigate whether such responses are endothelium-dependent. Using an in vitro micro-perfusion system, we isolated pig pulpal arterioles, cannulated and perfused them intraluminally, and monitored the diameter. Following equilibration, the vessels were contracted with 10(-5) M noradrenaline, and the effect of increasing doses of acetylcholine was determined. The influence of the muscarinic antagonist, atropine, or the loss of endothelial cell function following saponin treatment was also determined. Acetylcholine induced a dose-dependent vasodilation, reaching 94.6+/-1.4% (n = 22) of the uncontracted diameter at 10(-4) M. The vascular relaxation effect of acetylcholine was abolished in the presence of atropine, and by saponin treatment. Analysis of these data suggests that, in the pig, the acetylcholine-induced vasodilation of incisor pulpal arterioles is endothelium-dependent and mediated by muscarinic receptors.

Acetylcholine↗

PubMed2001

Comparison of the vasoactive effects of the docosanoid unoprostone and selected prostanoids on isolated perfused retinal arterioles.

PURPOSE: To compare the vasoactive properties of the docosanoid unoprostone, its free acid, and different members of the prostanoid family on isolated perfused pig retinal arterioles to assess their potential to modulate retinal blood flow. METHODS: Segments of porcine retinal arterioles were dissected, cannulated, and perfused, and their diameter monitored during either intraluminal or extraluminal application of increasing doses (10(-10)-10(-4) M) of either the docosanoid unoprostone isopropyl and its free acid or of selected prostanoids: prostaglandin (PG) F(2alpha) and thromboxane A(2) analogue (U46619). Studies were performed on arterioles in their uncontracted state, and also during precontraction with endothelin-1 (10(-9) M). The significance of any induced change in vessel diameter was assessed in relation to the initial vessel diameter or, in the case of endothelin-1 administration, to the contracted diameter with endothelin-1 alone. RESULTS: In normal-tone arterioles without endothelin-1 contraction, PGF(2alpha) and U46619 both produced a potent dose-dependent contraction, but neither unoprostone isopropyl nor unoprostone free acid had a significant vasoactive effect. In endothelin-1-contracted arterioles, U46619 produced further contraction, PGF(2alpha) produced a slight vasodilatation, and unoprostone isopropyl and its free acid produced a pronounced dilatation. CONCLUSIONS: Of the agents tested, unoprostone isopropyl and its free acid were the most potent vasodilators of endothelin-1-contracted pig retinal arterioles. Members of the prostanoid family demonstrated a different effect on the diameter of isolated retinal arterioles compared with the docosanoids. The potential therefore exists for the docosanoid unoprostone to have a beneficial effect on retinal blood flow in addition to any reduction in intraocular pressure.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed2000

Continued progression of retinopathy despite spontaneous recovery to normoglycemia in a long-term study of streptozotocin-induced diabetes in rats.

BACKGROUND: This long-term (2.3 years) study determines the temporal relationship between systemic glucose levels and the progression of diabetic retinopathy during the natural course of streptozotocin-induced diabetes in rats. METHODS: Of 367 rats, 200 were randomly assigned into a group injected with streptozotocin (50 mg.kg(-1)) and 167 into a control group. Subsets of the rats were killed at 6, 28, 40, 65, 90 and >100 weeks post induction to allow the severity of retinopathy to be assessed quantitatively and qualitatively by trypsin digests of the retinal vasculature. Concurrently blood glucose, body weight and death rate were monitored. RESULTS: Three glycemic phases were observed in the streptozotocin rats. In phase 1 (0 to 36-40 weeks) hyperglycemia was established and maintained. In phase 2 (36-40 to 84-90 weeks) normoglycemia was restored, and maintained during phase 3 (84-90 to 120 weeks). Control rats were normoglycemic throughout. The retinal microangiopathy was marked at 28 weeks during phase 1, developed more slowly in phase 2 and continued to worsen with loss of capillaries in all retinas and saccular microaneurysms present in 50% of retinas in phase 3. Cumulative death rate in streptozotocin rats also followed three phases, with maximum vulnerability occurring between 28 and 40 weeks. Body weight was significantly lower in streptozotocin rats throughout, increasing slowly in phase 1, then more rapidly during and after spontaneous glycemic recovery. CONCLUSION: The worsening retinopathy, despite sustained recovery to normoglycemia, implies that good glucose control alone does not stop the progression of the retinal microangiopathy at this late stage.

Animals↗

PubMed2000

Acetylcholine-induced relaxation in rat ocular vasculature.

Endothelial cell function is often evaluated by the assessment ofendothelium-dependent relaxation to acetylcholine. The purpose of this study was to characterize the acetylcholine-induced vasodilator responses in the intact ocular vasculature tree in isolated perfused rat eyes. At a fixed perfusion flow rate (5 microl/min), the resultant perfusion pressure reflected the total vascular resistance of the perfused vasculature. The baseline vascular resistance, and hence perfusion pressure, was manipulated by perfusion with high concentrations of potassium Krebs (60, 90, or 124 mM). The response to bolus administration of acetylcholine (10(-8) to 10(-4) M) was then assessed over a range of perfusion pressures. Acetylcholine induced a dose-dependent relaxation response which was larger in magnitude with increased levels of induced vascular tone. The relationship between the size of the acetylcholine-induced response and the baseline perfusion pressure was essentially linear with a correlation coefficient of 0.86 at 10(-5) M and of 0.88 at 10(-4) M acetylcholine. Our results suggest that, in the isolated perfused rat eye, the initial vascular tone has to be considered when evaluating endothelial cell function by acetylcholine-induced relaxation.

Acetylcholine↗

PubMed2000

Intraretinal oxygen levels before and after photoreceptor loss in the RCS rat.

PURPOSE: To measure the intraretinal oxygen environment at different stages in the Royal College of Surgeons (RCS) rat model of retinal degeneration to determine whether changes in oxygen level are an important aspect of the disease. METHODS: Oxygen-sensitive microelectrodes were used to measure oxygen tension as a function of depth through the retina of anesthetized, mechanically ventilated RCS rats at ages ranging from postnatal day (P)20 to P104. The oxygen profiles were correlated with histologic observations of the cellular changes within the dystrophic retinas and compared with those in RCS-rdy(+) control animals and published values in normal mature rats. RESULTS: Although the youngest rats studied exhibited some differences in intraretinal oxygen distribution compared with mature animals, the distribution in dystrophic RCS rats at P20 was not significantly different from that in age-matched control subjects. However, the intraretinal oxygen distribution in dystrophic RCS rats was clearly affected after approximately P30, reflecting a loss of photoreceptor oxygen consumption consistent with histologic observations. In contrast, oxygen uptake by the inner retina was still evident long after the loss of photoreceptors was essentially complete. CONCLUSIONS: There was no significant tissue hypoxia during photoreceptor degeneration in the dystrophic RCS rat. The changes in intraretinal oxygen distribution are consistent with the loss of outer retinal oxygen uptake but the preservation of inner retinal oxygen metabolism.

Animals↗

PubMed1999

Systemic and ocular vascular roles of the antiglaucoma agents beta-adrenergic antagonists and Ca2+ entry blockers.

This review addresses whether the antiglaucoma agents beta-adrenergic antagonists and Ca2+ entry blockers cause vasoactive effects in the retinal and other ocular vasculatures, as they do in other tissues. The potent vasodilating effects of Ca2+ entry blockers on ocular vessels have recently been demonstrated in in vivo and in vitro studies, implying that the maintenance of ocular vascular tone relies almost exclusively on extracellular Ca2+. Ca2+ entry blockers may potentially play a role in relaxing the retinal, long posterior ciliary, and ophthalmociliary arteries to improve the ocular circulation in vascular diseases in which there is considerable vascular tone present. The beta-adrenergic antagonists are discussed with reference to their antihypertensive role, their effect on other vascular beds, and finally what is known of their effect in the ocular vasculature. The emerging evidence that particular selective beta-adrenergic antagonists, such as betaxolol, are also potent Ca2+ channel entry blockers in other vascular beds is presented. Betaxolol has been shown to induce vasodilatation in the retinal and other ocular vascular beds, although studies have shown that beta1-adrenergic receptors are sparse in these vascular beds. This implies that an alternative mechanism must be responsible for betaxolol-induced vasodilatation. Evidence is presented that betaxolol vasodilates via its potent Ca2+ channel entry blocking properties, and its potency and ability to vasodilate are compared with those of nimodipine and timolol, as well as with those of other Ca2+ channel entry blockers. Important areas for future research in this area are discussed.

Adrenergic beta-Antagonists↗

PubMed1999

Intraretinal oxygen distribution in the rat with graded systemic hyperoxia and hypercapnia.

PURPOSE: To describe the nature of oxygen level changes in specific layers in the rat retina under graded levels of systemic hyperoxia, with and without hypercapnia. METHODS: Oxygen-sensitive microelectrodes were used to measure oxygen tension as a function of depth through the retina of anesthetized, mechanically ventilated rats. Breathing mixtures were manipulated to produce stepwise increments in systemic oxygen levels, with or without 5% CO2. Retinal arteriovenous oxygen differences were also measured as an indicator of oxygen delivery through the retinal circulation. Systemic blood gas levels were measured under each condition. RESULTS: Hyperoxia increases PO2 throughout the retina to a varying extent in different retinal layers, with the increase more pronounced in the outer retina than in the inner retina. Simultaneous hypercapnia results in further increases in retinal oxygen levels. The lowest intraretinal oxygen level was consistently found in the inner plexiform layer (IPL), between the two capillary layers that support this region. There was a greater than fourfold increase in oxygen supply from the choroid with hyperoxia but, remarkably, the retinal circulation continued to provide a net delivery of oxygen to the retina. CONCLUSIONS: Hyperoxia results in a significant but nonuniform increase in oxygen level in all layers of the rat retina, which is augmented by hypercapnia. The persistence of a minimum oxygen level in the IPL, despite the dramatic increase in oxygen flux from the choroid, suggests that oxygen consumption increases significantly in the IPL under hyperoxic conditions.

Animals↗

PubMed1999

Light and choroidal PO2 modulation of intraretinal oxygen levels in an avascular retina.

PURPOSE: To determine the influence that choroidal oxygen level and outer retinal oxygen demand have on oxygen availability to the inner retina when the choroid is the only source of retinal oxygenation. This condition prevails in avascular retinas and in vascularized retinas suffering vascular occlusion. METHODS: Oxygen-sensitive microelectrodes were used to measure the oxygen tension as a function of depth in the naturally avascular retina of anesthetized and mechanically ventilated guinea pigs (n = 6). Choroidal PO2 was manipulated by varying the ventilation gas mixture, and outer retinal oxygen consumption was modulated by light-dark adaptation. Individual PO2 profiles were fitted to a multilayer mathematical model of PO2 distribution, and pairs of profiles at different choroidal PO2 levels, or under light and dark conditions, were fitted to an intraretinal PO2 difference model. Both models reflect the purely choroidal supply of retinal oxygenation. RESULTS: An increase in choroidal PO2 produced an equivalent increase in all retinal layers. Light induced a decreased oxygen consumption in the region of the inner segments of the photoreceptors, which resulted in a significant increase in PO2 in this layer, flowing on unattenuated to all inner retinal layers. The intraretinal PO2 distribution and the light- and ventilatory-induced changes in PO2 were consistent with theoretical predictions of the mathematical models. CONCLUSIONS: The present experimental studies confirm that when the choroid is the only source of retinal oxygenation, the full effect of increased choroidal oxygen level or reduced uptake in the outer retina passes through to the inner retinal layers if the oxygen utilization by the inner retina remains constant.

Animals↗

PubMed1998

Effect of betaxolol, timolol and nimodipine on human and pig retinal arterioles.

This study tested the hypothesis that the beta-adrenergic antagonists betaxolol and timolol, cause retinal arteriolar vasodilatation in addition to their ability to reduce intraocular pressure (IOP), and compared their vasodilatory ability with that of a known Ca2+ channel entry blocker nimodipine in donor human and pig isolated perfused retinal arterioles. This study was performed using a microperfusion technique specifically established to allow investigations in arterioles as small as the first order human and pig retinal arterioles (approximately 100 microns diameter). The scarcity of viable human tissue was overcome by the successful development of controlled rate freezing and cryopreservation techniques which were able to preserve the vascular responsiveness of the retinal arterioles, thus enabling multiple experiments to be performed on segments of retinal arterioles from each individual donor eye. Furthermore, relaxation by acetylcholine in noradrenaline contracted pig retinal arterioles showed that endothelial cell function was well maintained after cryopreservation (n = 8). Baseline diameters of retinal arterioles used in the main studies were: cryopreserved human 92.3 +/- 3.4 microns (n = 44), fresh pig 94.7 +/- 2.2 microns (n = 42), and cryopreserved pig 94.3 +/- 2.3 microns (n = 30). Precontraction with extraluminal endothelin-1 (ET-1) 10(-9) M reduced the diameters to 74.3 +/- 0.9%, 71.6 +/- 1.6% and 72.5 +/- 0.9% respectively. Intraluminally applied nimodipine and betaxolol caused a significant dose dependent dilatation (P < 0.001) in human retinal arterioles with a threshold of 10(-12) M. Timolol did not produce a significant dilatation in human arterioles. Timolol produced a small but significant dilatation in fresh and cryopreserved pig arterioles but the dilatation with betaxolol and nimodipine was significantly larger. The nimodipine and betaxolol dose response curves were not significantly different in human arterioles, but nimodipine produced significantly greater dilatation than betaxolol (P < 0.001) in fresh and cryopreserved pig arterioles. Both nimodipine and betaxolol were significantly more effective vasodilators than timolol (P < 0.001) in human and pig retinal arterioles.

Adrenergic beta-Antagonists↗

PubMed1998

Intracellular structures of retinal vascular endothelium in normal and early diabetic rats.

PURPOSE: To determine whether the arrangement of microfilaments in retinal vascular endothelium is altered in early diabetes. METHODS: F-actin and nuclei of retinal vascular endothelial cells of normal and diabetic (28 weeks postinduction) rats were examined using confocal microscopy. RESULTS: An increase in the incidence of aberrant F-actin bundle arrangement in the diabetic retinal arteriole was observed, but there was no disruption of peripheral border F-actin. The diameter of superficial capillaries was increased in diabetic rats. CONCLUSION: These changes may be related to the endothelial dysfunction demonstrated in a previous pharmacological study.

Actins↗

PubMed1998

Robotic ocular ultramicrosurgery.

BACKGROUND: There is an increasing need for improved microsurgical techniques in the eye. Delivery of small quantities of chemicals or cells into specific retinal locations, for example, cannot be achieved with hand-held instruments. The present paper describes the design principles used in the development of a robotic ocular ultramicrosurgical system and the results from preliminary animal trials. METHODS: We have developed a robotic ocular ultramicrosurgical system and a range of instruments for specific intraocular applications. RESULTS: We have successfully used the system for intravascular (< 70 microm) drug delivery, implantation of microdrainage devices and the intraretinal manipulation of microelectrodes with minimal damage. CONCLUSION: A clinically usable system using the same principles appears feasible.

Animals↗