Light-induced changes in retinal oxygen consumption.
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Animals↗
Biomedical subjects
D Y Yu
Publications and source records attributed to D Y Yu.
Enhancement of mechanical strength of poly(2-hydroxyethyl methacrylate) sponges.
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Animals↗
Optimal conditions required for the creation of an iatrogenic chorioretinal venous anastomosis in the dog using argon green laser photocoagulation.
We have previously reported iatrogenic retinal to choroidal vein anastomosis, developed as a potential method of by-passing the site of obstruction to venous outflow in retinal venous occlusion in dogs (1), and in rats (2). In order to minimise tissue damage to the retina and choroid and increase the rate of success in these experiments, we investigated in the dog model the factors that would promote an anastomosis and compare the effects of three different power levels. A small spot size (50 microns) argon green laser beam of 514 nm at power levels of 0.5w, 1.5w and 2.5w were used. Spaced serial sections from each lesion were examined by light and by transmission electron microscopy. Morphometric measurements of the corresponding retinal pigment epithelium (RPE)/glial scar was computed using IBMPC digitising pad and sigma scan software and the extent of tissue damage at the different power levels assessed. At the lowest power level of 0.5w the damage to the retina was mild and there was an absence of anastomosis formation. At the 1.5w power level an anastomosis formed in 40% of the lesions. At the highest power level of 2.5w a 71% rate of success was obtained however, the damage to the retina tended to be severe. The results of this study also indicate that disruption of Bruch's membrane and vein rupture at the time of irradiation are essential for anastomosis formation, which may be further enhanced by necrotic tissue, retinal pigment epithelial and glial scar formation and inflammation. These findings are useful in establishing optimal conditions for the creation of a chorioretinal venous anastomosis, for consideration in human trials.
Anastomosis, Surgical↗
The influence of cerebrospinal fluid pressure on the lamina cribrosa tissue pressure gradient.
PURPOSE: To measure the tissue pressure gradient through the optic disk and to determine the relationship between intraocular, cerebrospinal fluid, and retrolaminar tissue pressures. The relationship of optic nerve subarachnoid space pressure to intracranial cerebrospinal fluid pressure also was explored. METHODS: Micropipettes coupled to a pressure transducer were passed through pars plana and vitreous to enter the optic disk in the anesthetized dog. Using a micromanipulator, pipettes penetrated the optic disk in steps while pressure measurements were taken. In some animals, pipettes also were passed into the optic nerve subarachnoid space. Lateral ventricle cerebrospinal fluid pressure, intraocular pressure, and arterial blood pressure were measured concurrently, and the effect of raising CSF pressure was explored. RESULTS: Retrolaminar tissue pressure was largely dependent on the surrounding cerebrospinal fluid pressure, which was on average 8.6 +/- 3.5 mm Hg (SD, n = 8) higher, and was independent of intraocular pressure. Most (85% +/- 15% [SD, n = 8]) of the pressure drop between intraocular pressure and retrolaminar pressure occurred across the anterior 400 microns of disk tissue. When the intraocular pressure was 21 mm Hg and the cerebrospinal fluid pressure was zero, retrolaminar tissue pressure averaged 7 mm Hg and the translaminar pressure gradient was 3.08 +/- 0.29 mm Hg/100 microns tissue (SD, n = 3). Optic nerve subarachnoid space pressure was equivalent to lateral ventricular pressure. CONCLUSIONS: These results show that cerebrospinal fluid pressure largely determines retrolaminar tissue pressure; hence, along with intraocular pressure, it is of major importance in setting the translaminar tissue pressure gradient. Results also demonstrate hydrostatic continuity between the optic nerve subarachnoid space and the lateral ventricle. That the translaminar pressure gradient can vary independently of intraocular pressure may be of importance in understanding the pathophysiology of glaucoma.
Animals↗
Intravitreal perfluorocarbon and oxygen delivery in induced retinal ischaemia.
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Acute Disease↗
Intraretinal oxygen distribution in rats as a function of systemic blood pressure.
Differential responses to induced changes in systemic blood pressure (BP) at different layers of both the retinal and choroidal vasculature were observed, by monitoring localized PO2 as a function of depth, in the retina and choroid of the rat eye using oxygen-sensitive recessed microelectrodes. Visual and electrophysiological localization of the microelectrode tip allowed the oxygen distribution to be related to the positions of the vascular beds of the retina and choroid. Highly reproducible intraretinal PO2 profiles were achieved. The relationship between PO2 and systemic BP was linear in the deep capillary layer of the retina (PO2 = 0.17 x BP - 2.63) and in the choriocapillaris (PO2 = 0.21 x BP + 2.95), whereas it was nonlinear in the superficial retinal capillary layer [PO2 = 40.01/[1 + (BP/66.22)-1.22]] and deep choroid [PO2 = 83.82/[1 + (BP/124.61)-0.87]]. The minimum PO2 occurred between the two retinal capillary beds, and a PO2 gradient was evident in the choroid. The contrasting responses of different layers of the two circulations reflect different blood flow control mechanisms not evident when studying the circulations as a whole.
Animals↗
Adrenergic and nitrergic neurotransmitters are released by the autonomic system of the pig long posterior ciliary artery.
The role played by adrenergic, muscarinic and nitric oxide putative neurotransmitters released from autonomic nerve endings onto the pig proximal long posterior ciliary artery (LPCA) was determined. The proximal LPCA in the pig usually supplies both the uveal and retinal circulations. In this study, in vitro ring segments of the artery, passively stretched and with noradrenaline-induced tone, were neurogenically stimulated (NS) using electrical field stimulation with 5-sec trains of 0.2 msec pulses. NS produced a frequency dependent contraction in all vessels which was completely abolished by 10(-6) M tetrodotoxin. 40 Hz stimulation was used throughout the study as it produced a maximal NS contraction. 10(-5) M guanethidine abolished the NS-induced contraction and revealed a NS-induced relaxation, as did the alpha adrenergic blocker, phentolamine, in vessels passively stretched. The beta adrenergic blocker, propranolol, only slightly reduced the NS-induced constriction. In vessels pre-contracted with noradrenaline, NS produced a relaxation (D) which was proportional in magnitude to the tone (C) viz. D = (0.30 +/- 0.04).C + (0.24 +/- 0.06). The muscarinic blocker, atropine, had no effect on the NS-induced relaxation, implying that it is a non-adrenergic, non-cholinergic mediated system. Incubation with Nw-nitro-L-arginine methyl ester reduced the NS-induced relaxation to 48% of its control value, a reduction which was reversed in the presence of excess L-arginine. Damage to endothelial cell function did not reduce the NS-induced relaxation. It is concluded that the autonomic innervation of the proximal LPCA releases both contraction and relaxation neurotransmitters. Contraction is mediated by an alpha adrenergic neurotransmitter. At least two neurotransmitters mediate relaxation, one of which is probably nitric oxide. There is no functional evidence for the release of beta adrenergic neurotransmitter from the sympathetic system or acetylcholine from the parasympathetic system.
Acetylcholine↗
Significance of Bruch's membrane in the creation of iatrogenic chorioretinal venous anastomosis.
Iatrogenic retinal to choroidal vein anastomoses, as a method of bypassing retinal venous occlusions has been reported in dogs in which Bruch's membrane is poorly formed. In order to determine whether chorioretinal venous anastomoses can be induced in an animal with a Bruch's membrane that is well developed as in humans, pigmented rats were chosen. A high intensity, small spot size argon green laser beam of 514 nm was used to induce the anastomosis. Three out of 5 rat eyes developed a retinal vein to choroidal vein anastomosis. The success rate of iatrogenic retinal to choroidal vein anastomoses in the rat was comparable to that obtained in the dog. This study suggests that Bruch's membrane was not significant in the creation of an iatrogenic chorioretinal venous anastomosis.
Anastomosis, Surgical↗
Vasoactivity of intraluminal and extraluminal agonists in perfused retinal arteries.
PURPOSE: To evaluate the vasoactive response of isolated perfused arteries of the pig to K+ and adrenergic agonists and to compare the effects of intraluminal (IL) and extraluminal (EL) drug delivery. METHODS: A new microperfusion system was developed, in which short lengths of porcine retinal arteries (outer diameter 90.4 +/- 2.7 microns) were cannulated at both ends and perfused at a controlled rate (5 microliters/min) with outflow through a single side branch. The diameter of the vessel and the intraluminal pressure were monitored, and the effect of intraluminally and extraluminally applied agonists was determined. Endothelial cell function and the integrity of the blood retinal barrier was verified. RESULTS: Consistent vasoactive responses were obtained from most vessels. The resting diameter of the vessel was not greatly influenced by changes in flow rate or intraluminal pressure over the physiological range. Adrenaline and noradrenaline caused dose-dependent contractions, which were larger when applied intraluminally than they were when applied extraluminally. The largest contraction for adrenaline was 19.0% +/- 2.1% (n = 13) IL and 8.4% +/- 1.5% (n = 13) EL, and for noradrenaline, 17.8% +/- 1.9% (n = 13) IL and 6.8% +/- 1.1% (n = 13) EL. The IL contraction to 124-mM K+, 19.0% +/- 1.6% (n = 21), was also greater than that for EL application, 5.0% +/- 1.0% (n = 13). We found that the existence of myogenic contractions was restricted to the special case in which vessels with no branches were pressurized under zero flow conditions. CONCLUSIONS: Pig retinal arteries exhibited asymmetry in their responses to adrenergic agonists and K+, with contractions significantly larger when the drug was applied to the intraluminal surface rather than the extraluminal surface. This asymmetry may reflect an important property of retinal vessels. Microperfusion systems of this type may prove valuable in developing a better understanding of control mechanisms in retinal circulations.
Adrenergic alpha-Agonists↗
Effects of extracellular pH on agonist-induced vascular tone of the cat ophthalmociliary artery.
PURPOSE: To test whether changes in extracellular pH (pHe) in an in vitro preparation of the cat ophthalmociliary artery affect passive tone and agonist responses and whether the endothelial cells are mediators of any pH-induced effect. This will determine the ability of the ophthalmociliary artery to influence retinal and choroidal blood flow in response to metabolic stimuli. METHODS: The isometric tension generated by isolated ring segments preactivated by prostaglandin F2 alpha (PGF2 alpha), noradrenaline (NA), or 40 mM K+ was measured as the pHe of the bathing solution was changed stepwise from 6.0 to 8.0 by adjusting the bathing bicarbonate concentration in preparations with and without functioning endothelial cells. RESULTS: PGF2 alpha produces a concentration-dependent contraction that is insensitive to an alkaline shift from control pHe (7.4) in the bathing medium. For acidic shifts to pHe 7.0, there is no significant change in the magnitude of the PGF2 alpha contraction, whereas at pHe 6.0, the PGF2 alpha contraction is reduced to 23 +/- 4% (n = 23) of its value at pHe 7.4. Threshold response concentration remains unaffected. Deliberate damage to the endothelial cells does not significantly affect the magnitude of the 10(-5) M PGF2 alpha response at pHe 7.4 nor the effect of acidic pH on this response. The 10(-5) M NA response is reduced in a graded fashion to acidic shifts to pH 7.0 and 6.0 (40 +/- 4% [n = 23]) and also to alkaline shift to pH 8.0 (22 +/- 5% [n = 23]) when compared to the induced tension at pHe 7.4. For the acidic shift only, endothelial cell damage causes a further significant reduction in the NA response to 20 +/- 3% (n = 5). For vessels contracted with K(+)-Krebs solution, there is a small but significant reduction in response at pHe 6.0 to 84 +/- 6% (n = 25), whereas for pHe 8.0 there is a much larger reduction to 45 +/- 5% (n = 24). All pHe-induced relaxations of K+ are endothelium independent. Passive tension is unaffected by all pHe manipulations. CONCLUSIONS: Vessel responses to vasoactive agents are selectively mediated by pHe changes. Major acidic shifts cause reduced responses (relaxation) to NA, PGF2 alpha, or K+, whereas only vessels preactivated with NA and K+ relax to alkaline shifts. This implies that NA or K+ induced vascular responses are maximal close to neutral pHe with major shifts from neutrality in either the acidic or alkaline direction causing a reduced response. These results imply that the ophthalmociliary artery probably does not play a major role in controlling ocular blood flow in response to pHe changes within the normal metabolic range, but it may become important in ischemic conditions.
Animals↗
Oxygen reactivity of the feline isolated ophthalmociliary artery.
PURPOSE: The goal of this study was to investigate the modulating role of oxygen tension on noradrenaline (NA) and KCl responses in the ophthalmociliary artery and to ascertain whether these effects are mediated by the endothelial cells. METHODS: The isometric tension generated by myograph ring segments activated by NA or KCl was measured as the PO2 of the bathing solution was decreased in discrete steps from 506.1 +/- 16.0 mmHg to 29.4 +/- 1.4 mmHg in preparations with and without endothelial cells. RESULTS: Vessels pre-activated with K+ Krebs solution were insensitive to oxygen tensions between 506.1 +/- 16.0 mmHg and 124.6 +/- 4.2 mmHg. Lower PO2s caused a graded and increasing contraction that reached 176 +/- 12% of the contraction at the highest PO2. Vessels pre-activated with NA had a dichotomous response to reductions in oxygen tension: 44% of vessels showed a graded contraction, whereas a graded relaxation was observed for the remaining 56% of vessels as bath PO2 was reduced. In all cases, a functional endothelium was demonstrated. However, deliberate disruption of the endothelium caused all vessels pre-activated with NA to exhibit a consistent graded contraction for PO2s below 124.6 +/- 4.2 mmHg, similar to that observed for endothelial intact vessels pre-activated with K+ Krebs. The acetylcholine dose-response curve and passive tension were not affected by changes in oxygen tension. CONCLUSIONS: Endothelial cells modify the intrinsic smooth muscle response to a gradual reduction in PO2 by releasing relaxing and contracting factors, causing the observed dichotomous response in NA-activated vessels. However, the KCl-induced response is modulated only by low oxygen tensions.
Animals↗
Retinal blood flow by hydrogen clearance polarography in the streptozotocin-induced diabetic rat.
PURPOSE: The authors compared retinal blood flow in rats after 5 weeks of streptozotocin (STZ)-induced diabetes with that in age-matched control animals. METHODS: The flow measurements were based on the hydrogen clearance technique and the intraocular placement microelectrodes at the surface of the retina. The hydrogen was delivered by bolus injection (100 microliters) of hydrogen-saturated saline into the ipsilateral carotid artery using a cannula through the lingual artery. The rats were anesthetized and artificially ventilated. Care was taken to match the systemic blood pressure and blood gases in the two groups. RESULTS: The mean retinal blood flow in the STZ group after 5-6 weeks duration of hyperglycemia was 487 +/- 59 ml/min/100g (standard error) compared with 330 +/- 16 ml/min/100 g in the age-matched controls. The variation in retinal blood flow was far more pronounced in the STZ group, even in different locations in the same eye. Changes in fundus appearance were also noted, with second-order arterioles being more apparent and the retina more "pinkish" in appearance in the STZ animals. CONCLUSIONS: The mean retinal blood flow in the region of retina studied in the two groups was significantly higher in the STZ animals than in age-matched controls. The increased heterogeneity of retinal blood flow may reflect a disruption to the normal blood flow control mechanisms in the retina after only 5 weeks of STZ-induced diabetes.
Animals↗
Intravitreal and intraretinal oxygen tension in the rat eye.
We have successfully measured the intravitreal and intraretinal oxygen distribution in normal rats, during both normoxia and hyperoxia. The feasibility of such measurements in the very small rat eye has opened up the opportunity for the use of the many rat models of vascular disease in physiological experiments of retinal oxygen supply and consumption.
Animals↗
Oxygen tension and blood flow in the retina of normal and diabetic rats.
The use of microelectrode techniques for studying oxygen distribution and blood flow in the eye of a physiologically well maintained rat provides a very convenient model in which to study oxygen supply to the retina. The availability of rat models of vascular disease such as diabetes and hypertension, and the existence of several models of retinal degeneration, make studies of oxygen supply in the rat eye of particular relevance. The experiments reported in this paper demonstrate changes in oxygen distribution and blood flow very early in STZ induced diabetes. Thus, we have established a preparation in which the role of changes in oxygen supply can be correlated with the pathological events that are apparent later in the disease.
Animals↗
Pharmacological and mechanical heterogeneity of cat isolated ophthalmociliary artery.
The mechanical, histological and pharmacological properties of the isolated cat ophthalmociliary artery are reported and compared for passively stretched ring segments from three locations on the artery. Ring segments were mounted in a modified myograph system after the method of Hogestatt, Andersson and Edvinsson (1983, Acta Physiol Scand. 117, 49-61) and comparative length tension curves were measured. The most distal segment (DOA), nearest the eye, developed by far the smallest maximal tension compared to the middle segment (MOA) and the most proximal segment (POA), despite the fact that lumen diameters were similar. All segments displayed a phasic and tonic component in response to passive stretching and during activation with K(+)-Krebs. Cumulative contractile dose-response curves were measured for nine agonists: histamine (HIS), 5-hydroxytryptamine (5-HT), dopamine (DOPA), adrenaline (A), noradrenaline (NA), tyramine (TYR), phenylephrine (PHE), isoproterenol (ISOP) and xylazine (XYL) and the maximum active tension developed at a concentration of 10(-3) M was compared with that for 0.124 M K(+)-Krebs. The order of contraction magnitude in the three segments was: POA, HIS much greater than Kmax much greater than NA greater than A greater than DOPA greater than PH = TYR greater than 5-HT = ISOP greater than XYL; MOA, Kmax much greater than NA much greater than A = HIS much greater than DOPA greater than ISOP = PHE greater than TYR = 5-HT greater than XYL; DOA, Kmax much greater than NA greater than A greater than HIS = DOPA greater than ISOP greater than PHE = 5-HT greater than XYL = TYR. Pre-activation did not produce relaxation in response to histamine and isoproterenol. Testing with specific alpha 1 and beta antagonists supported the presence of alpha 1 receptors but not beta receptors. It is concluded that functional HIS, alpha 1 and 5-HT receptors are present and that the ophthalmociliary artery is heterogeneous in its response to HIS, with the POA segment producing the largest responses. The magnitude of the contractile responses to A and NA grew with increasing passive tension, whereas the response to histamine was independent of passive tension.
Adrenergic Agonists↗
Relaxation effects of diltiazem, verapamil, and tolazoline on isolated cat ophthalmociliary artery.
This study investigates the ability of an alpha 1-adrenergic blocker, tolazoline, two Ca2+ entry channel blockers, verapamil and diltiazem, acetylcholine and Ca(2+)-free solutions to relax alpha 1-adrenergically activated cat ophthalmociliary artery ring segments. The form of a contraction elicited with adrenaline, noradrenaline or phenylephrine was shown to depend on the passive tension set. As passive tension was increased, which is equivalent to increasing blood pressure in vivo, the alpha 1-adrenergic elicited contraction became more sustained. Incubation with the Ca2+ channel blockers diltiazem and verapamil was ineffective in reducing the phasic response to the alpha 1-adrenergic agonists whereas addition of these blockers in increasing concentrations during a sustained adrenergic contraction caused a graded and significant relaxation. This implies that therapeutic use of Ca2+ channel blockers may act directly on the ophthalmociliary artery to inhibit the autonomic control of sustained tone in this vessel. Removal of exogenous Ca2+ from the bathing medium initially reduced the phasic component and eliminated the tonic component of the alpha 1-adrenergic contraction. Repeated exposure of the ring segment to Ca(2+)-free medium further reduced the phasic component elicited with alpha 1-adrenergic contraction. Pre-incubation with the alpha 1-adrenergic blocker Tolazoline reduced the alpha 1-adrenergic antagonist phasic response only at high concentrations (10(-4) M), whereas Tolazoline applied during the tonic phase was an effective relaxant at lower concentrations. Acetylcholine added to the bath during an alpha 1-adrenergic contraction induced relaxation at low concentrations and contraction for higher concentrations. The relaxation was eliminated by removal of the endothelial cell layer. These data support the notion that the phasic component of an alpha 1-adrenergic contraction is mainly dependent on intracellular Ca2+ stores whereas the tonic component relies almost exclusively on extracellular Ca2+. It is suggested that Ca2+ channel blockers and alpha 1-adrenergic antagonists may potentially play a role in relaxing the ophthalmociliary artery to improve the ocular circulation in vascular diseases in which there is considerable vascular tone present.
Animals↗
Induced chorioretinal venous anastomosis in experimental retinal branch vein occlusion.
Iatrogenic retinal vein to choroidal vein anastomoses were created using laser photocoagulation in six of seven dog eyes in which a partial branch retinal vein occlusion had previously been created photochemically. A similar attempt to create an anastomosis was made in six control eyes in which no branch vein occlusion was present. In the eyes in which a branch retinal vein had been created, a venous chorioretinal anastomosis appeared to be present by 3 to 6 weeks. In three control eyes similar venous anastomosis was created; however this took 6 to 8 weeks to develop and was of much smaller calibre than the one that developed in the presence of a partial branch retinal vein occlusion. No adverse complications were noted in the period of the study (3 months). This study demonstrates that chorioretinal venous anastomoses can be created and may be of use in the treatment of partial retinal vein occlusions that show signs of progression.
Anastomosis, Surgical↗
Comparison of hematologic parameters in normal and streptozotocin-induced diabetic rats.
Hematologic values are compared for normal and streptozotocin-induced diabetic rats after 6 weeks of induced diabetes. Most hematologic parameters were the same in the two groups except for blood glucose, glycated hemoglobin, and 2,3 diphosphoglycerate, all of which were elevated in the streptozotocin group. However the P50 (the PO2 at which the oxygen-carrying capacity of blood is 50% of maximal) remained normal. We hypothesize that a left shift in the oxyhemoglobin dissociation curve caused by the glycation of a small percentage of the hemoglobin is compensated by elevation in the 2,3-diphosphoglycerate which returns the P50 to normal values. This compensatory mechanism also occurs in some stages of human diabetes.
2,3-Diphosphoglycerate↗