Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0595921 (intraocular pressure)
11,750 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of intravenous administration of a calcium antagonist on the retinal microcirculation in rabbit eyes was examined with a laser speckle retinal microcirculation analyzer. Under general anesthesia, 40 micrograms/kg of nicardipine, a calcium antagonist, was injected intravenously in the nicardipine group, and 0.4 ml/kg of saline in the control group. A quantitative index of blood flow velocity, the normalized blur (NB) value, in a retinal area (0. 62 x 0.62 mm) free of visible vessels, was recorded at 1-minute intervals for the first 5 minutes and at 5 minute-intervals for the next 85 minutes. The retinal NB value in the nicardipine group was significantly greater than in the control group, averaging 119%, 115%, 111%, 112%, and 116% of the initial value at 65, 75, 80, 85, and 90 minutes after injection, respectively. The blood pressure in the nicardipine group decreased significantly from 1 to 20 minutes after injection. The pulse rate, arterial pH, partial CO2 pressure, partial oxygen pressure, body temperature and intraocular pressure did not show significant change during the experiment. These results suggest, for the first time, that nicardipine increases the blood flow velocity in the retinal microvasculature in the living eye.
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PMID:[Effect of calcium antagonist on retinal microcirculation evaluated with the laser speckle retinal microcirculation analyzer]. 815 80

Cyclocryocautery of different time duration was done on 52 rabbit eyes with the Syncron Optikon CO2 cryocoagulator. Postoperative studies of the ciliary body by light and electron microscopy and enzymatic histochemical analysis at various intervals revealed morphologic and metabolic changes in the epithelial cells that resulted in diminished aqueous humor formation and lowered intraocular pressure. 50 cases of glaucoma patients (54 eyes) were treated with cyclocryotherapy and followed up over 6 months, with a success rate of 72% in the advanced refractory patients and the pain was relieved in 85%. 8 of the ineffective eyes were performed additional cyclocryotherapy under a scleral flap, with good results in 5 eyes.
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PMID:[An experimental study of cyclocryocautery and its application on glaucoma patients]. 824 94

Organic sulfamates are a new variation to the carbonic anhydrase (CA) inhibitor structure-action relationship. Inhibitory activity is conferred by the classic sulfonamide group, but through linkage to the benzene ring by an oxygen. AHR-16329, a representative sulfamate, has an acidic (sulfonamide, pKa 8.9) and basic (imidazole, pKa 6.0) group and has desirable physicochemical properties for topical intraocular pressure lowering: good water solubility below pH 6.0, a CHCl3/buffer ratio of 0.5 at pH 7.0 and a Kl against CA-II of 7 nM. Inhibition of CO2 hydration is noncompetitive. When applied locally to the eye, AHR-16329 reaches significant levels in ocular tissues and fluids and reduces significantly intraocular pressure. Five percent concentration gives the greatest reduction, equivalent to systemic inhibitors; 2 and 5% have similar pressure x time duration. These studies expand structure-action relations in the field of CA inhibitors and the validity of developing topical CA inhibitors for treatment of glaucoma.
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PMID:Carbonic anhydrase inhibitory activity and ocular pharmacology of organic sulfamates. 843 14

This review describes the techniques to evaluate retinal neurodegeneration induced by excitatory amino acids and transient ischemia. Glutamate-induced neurotoxicity was examined in cultured rat cortical cells. Cultures obtained from the retinas of fetal rats were incubated in Eagle's minimal essential medium supplemented with 10% fetal calf serum or 10% horse serum at 37 degrees C in a humidified 5% CO2 atmosphere for 10-14 days. The neurotoxicity induced by glutamate was quantified by trypan blue exclusion. The viability of cultures was markedly reduced by a 10-min exposure to glutamate followed by incubation with glutamate-free medium for 1 hr. N-methyl-D-aspartate (NMDA)-induced retinal damage was examined in adult rats. Transverse sections of the retinas through the optic disk were stained with hematoxylin and eosin. A single intravitreal injection of NMDA damaged the ganglion cell layer and the inner plexiform layer without affecting the other retinal layers 7 days after injection. Retinal ischemia was induced by elevating the intraocular pressure for 45 min through the needle which was placed in the anterior chamber. Ischemia-induced retinal damage was inhibited by MK-801. These results indicate that the techniques described in this review can be employed to develop new drugs possessing neuroprotective action against neurodegeneration that occurs during retinal ischemia.
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PMID:[Techniques for evaluating neuronal death of the retina in vitro and in vivo]. 955 48

Glaucoma remains a major eye illness with unknown etiology. Although elevated intraocular pressure is clearly a major risk factor, vascular deficits may contribute to initiation and progression of glaucoma. When intraocular pressure is acutely elevated in healthy individuals, the resistance index (derived from the peak systolic and end-diastolic velocities and an indirect index of vascular resistance distal to the site of measurement) in the central retinal and posterior ciliary arteries increases progressively. This result implies that mechanical and vascular factors may be coupled in such a way that perfusion of the retina and optic nerve head may be influenced by changes in the intraocular pressure. Further, at night, when ophthalmic artery flow velocities fall as arterial blood pressure falls in glaucoma patients, the risk of disease progression may be increased. The constancy of these same flow velocities in age-matched healthy individuals points to a possible vascular autoregulatory defect in glaucoma. In addition, in normal-tension glaucoma, vasodilation (CO2 inhalation) normalizes retrobulbar arterial flow velocities, hinting that some vascular deficits in glaucoma may be reversible. Finally, Ca2+ channel blockade improves contrast sensitivity in patients with normal-tension glaucoma, who also show increased retrobulbar vessel flow velocities, a result suggesting that visual function loss may be linked to ocular ischemia. Emerging evidence points to a role of ischemia in the pathogenesis of glaucoma, suggesting that treatments designed to improve ocular blood flow may benefit glaucoma patients.
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PMID:Vascular aspects in the pathophysiology of glaucomatous optic neuropathy. 1041 46

The ciliary epithelium secretes aqueous humor, an intraocular fluid whose production is regulated in part by transmembrane signaling pathways including those mediated by G protein-coupled receptors. Many drugs, such as beta-adrenergic receptor (AR) antagonists and alpha2-AR agonists, are used to lower intraocular pressure by presumably decreasing fluid transport across this epithelium. Hence, our purpose was to establish a ciliary epithelial organ culture system suitable for the study of cell signaling pathways. A trypsin-mediated dissection method was established to isolate bovine ciliary epithelial sheets. These sheets were cultured in a 5% CO2 incubator. The quality was assessed by light microscopy, by protein analysis, and by the evaluation of epinephrine-mediated phosphoinositide turnover. The cultured epithelial explants were viable as evidenced by minimal trypan blue staining. The explants were composed primarily of nonpigmented cells and some pigmented cells, but no other ciliary body tissues were present on histology. Membrane preparations showed proteins with a distribution from 31 to 116 kDa. Epinephrine caused a dose-dependent increase in [3H]inositol phosphates (InsPs) accumulation with a maximal increase of two- to three-fold over basal levels. This epinephrine-mediated increase was inhibited by prazosin. We established an organ culture system of isolated bovine ciliary epithelium suitable for the study of transmembrane signaling pathways.
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PMID:Cell signaling in bovine ciliary epithelial organ culture. 1067 33

Hemodialysis, a useful treatment for patients with severely compromised renal function, has also unfavorable side effects. In the ophthalmologic area, a rise in intraocular pressure (IOP) during dialysis accompanied by ocular pain has been reported. In our study when measuring IOP, as well as serum osmolality and plasma CO2 pressure every 30 minutes during routine hemodialysis in renal failure patients with a normal aqueous outflow facility, the mean percent changes of IOP to the initial value showed no significant difference at any time, although the changes in serum osmolality decreased significantly. The mean percent changes of plasma CO2 pressure also did not show any significant difference during dialysis. In patients with a poor aqueous outflow facility, the mean percent changes of IOP increased significantly after 90 minutes, with the exception of the change at 180 minutes. The mean percent changes of serum osmolality decreased significantly after starting dialysis. A negative correlation in the mean percent change of IOP with that of serum osmolality was detected. The administration of an intravenous hyperosmotic agent prevented significant changes not only in serum osmolality but also in IOP. Therefore, it is considered that hemodialysis causes a decrease in serum osmolality, resulting in an osmotic gradient between the plasma and the intraocular fluids due to the presence of the blood-ocular barrier. Although the osmotic gradient draws water from the plasma into the eye, if there is no abnormal obstruction in the aqueous outflow pathway, an amount of aqueous humor matching the increase in intraocular fluid goes through the pathway out of the eye to maintain the normal level of IOP. In eyes with an obstructed aqueous outflow pathway, however, this compensatory mechanism of aqueous humor drainage does not work well, and results in an IOP elevation.
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PMID:[Intraocular pressure during hemodialysis]. 1073 23

The modulation of the enhanced release of [3H]glutamate following ischemia-like conditions was studied in rat hippocampal slices using a superfusion system. Ischemia was simulated by a glucose-free medium equilibrated with 95% N2 and 5% CO2. In this model the potential neuroprotective effects of several substances on [3H]glutamate release induced by ischemia-like conditions were investigated. Gabapentin-lactam (8-aza-spiro-5,4-decan-9-on; GBP-L) was synthesised and patented in our laboratory. GBP-L (100 microM) reduced the oxygen glucose deprivation-induced [3H]glutamate release by 42.5%, CI95=[33.4%, 51.5%]. The KATP channel antagonist glibenclamide (1 microM) blocked this effect completely. The high antagonist potency was reflected by an apparent pA2-value of glibenclamide of 8.3, CI95=[6.8, 9.4]. Minoxidil sulfate (10 microM), a KATP channel opener, mimicked the effect of GBP-L (inhibition by 22.8%, CI95=[13.2%, 32.5%]). Similarly to its lactam, also gabapentin (100 microM) reduced the oxygen glucose deprivation-induced [3H]glutamate release by 30.6%, CI95=[15.5%, 45.7%], whereas the "antiglutamatergic" drug riluzole was ineffective. GBP-L and gabapentin were also tested in an in vivo model of acute retinal ischemia in rats. The intraocular pressure was elevated for 1 h above the systolic blood pressure. In the control group, 17.5%, CI95=[13%, 22%], of retinal ganglion cells had survived after 2 weeks. GBP-L doubled the number of surviving ganglion cells up to 35%, CI95=[27%, 43%], while gabapentin had no effect. This difference between gabapentin and its lactam may be due to different pharmacokinetic properties: In contrast to the gamma-amino acid gabapentin, GBP-L is uncharged and therefore might diffuse more easily through biological membranes, e.g. the plasma membrane, to get access to an intracellular locus of action. Thus, the neuroprotective properties in vivo and the diminished oxygen glucose deprivation-induced [3H]glutamate efflux in vitro of the presumed KATP channel agonist GBP-L suggest that this substance might be therapeutically applied in pathological situations induced by a rise in extracellular glutamate and/or neuronal cell death.
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PMID:Gabapentin-lactam (8-aza-spiro[5,4]decan-9-on; GBP-L) inhibits oxygen glucose deprivation-induced [3H]glutmate release and is a neuroprotective agent in amodel of acute retinal ischemia. 1093 36

The autoregulatory capacity of the human retina is well documented, but the pressure-flow relationship of the human choroid is still a matter of controversy. Recent data, using laser Doppler flowmetry to measure choroidal blood flow, indicate that the choroid has some autoregulatory potential, whereas most data using other techniques for the assessment of choroidal hemodynamics indicate that the choroidal pressure-flow curve is linear. We used a new laser interferometric technique to characterize choroidal blood flow during isometric exercise. Twenty healthy subjects performed squatting for 6 min during normocapnia and during inhalation of 5% CO2 and 95% air. Ocular fundus pulsation amplitude, flow velocities in the ophthalmic artery, intraocular pressure, and systemic hemodynamics were measured in 2-min intervals. To gain information on choroidal blood flow fundus pulsation amplitude was corrected for changes in flow pulsatility using data from the ophthalmic artery and for changes in pulse rate. Ocular perfusion pressure was calculated from mean arterial pressure and intraocular pressure. The ocular pressure-flow relationship was calculated by sorting data according to ascending ocular perfusion pressure values. In a pilot study in 6 healthy subjects comparable ocular pressure flow relationships were obtained when choroidal blood flow was assessed with the method described above and with laser Doppler flowmetry. In the main study isometric exercise caused a significant increase in mean arterial pressure (56%, P < 0.001), pulse rate (84%, P < 0.001), and intraocular pressure (37%, P 0.004), but decreased fundus pulsation amplitude (-36%, P < 0.001). Significant deviations from baseline choroidal blood flow were observed only at ocular perfusion pressures >69% during normocapnia and 70% during hypercapnia. Our data indicate that during isometric exercise the choroid has a high capacity to keep blood flow constant despite changes in perfusion pressure and that this pressure-flow relationship is not altered by moderate changes in arterial carbon dioxide levels.
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PMID:Ocular hemodynamics during isometric exercise. 1116 91

The possible existence of transepithelial bicarbonate transport across the isolated bovine ciliary body was investigated by employing a chamber that allows for the measurement of unidirectional, radiolabeled fluxes of CO2 + HCO. No net flux of HCO was detected. However, acetazolamide (0.1 mM) reduced the simultaneously measured short-circuit current (I(sc)). In other experiments in which (36)Cl- was used, a net Cl- flux of 1.12 microeq. h(-1). cm(-2) (30 microA/cm(2)) in the blood-to-aqueous direction was detected. Acetazolamide, as well as removal of HCO from the aqueous bathing solution, inhibited the net Cl- flux and I(sc). Because such removal should increase HCO diffusion toward the aqueous compartment and increase the I(sc), this paradoxical effect could result from cell acidification and partial closure of Cl- channels. The acetazolamide effect on Cl- fluxes can be explained by a reduction of cellular H+ and HCO (generated from metabolic CO2 production), which exchange with Na+ and Cl- via Na+/H+ and Cl-/HCO exchangers, contributing to the net Cl- transport. The fact that the net Cl- flux is about three times larger than the I(sc) is explained with a vectorial model in which there is a secretion of Na+ and K+ into the aqueous humor that partially subtracts from the net Cl- flux. These transport characteristics of the bovine ciliary epithelium suggest how acetazolamide reduces intraocular pressure in the absence of HCO transport as a driving force for fluid secretion.
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PMID:Model of ionic transport for bovine ciliary epithelium: effects of acetazolamide and HCO. 1135 Jul 47


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