Biomedical subjects

C B Toris

Publications and source records attributed to C B Toris.

17 recordsLinked to original sources

PubMed1997

Effects of exogenous prostaglandins on aqueous humor dynamics and blood-aqueous barrier function.

Topical prostaglandins (PGs) are very effective at reducing intraocular pressure (IOP) in a variety of animals and in humans with relatively few side effects. The mechanisms of action of several PGs, their prodrugs and analogues have been studied in rabbits, cats, monkeys and humans. PGF2 alpha and its analogues evaluated in monkeys include PGF2 alpha-tromethamine salt, PGF2 alpha -isopropylester (-IE), S-1033, PhXA34, PhDH100A and latanoprost (PhXA41). Aqueous flow and outflow facility are either increased or remain unchanged by these agents. PGF2 alpha-IE, PHXA34, PhDH100A and latanoprost increase uveoscleral outflow, accounting for most of the IOP reduction. PGA2 in cats increases aqueous flow and outflow facility, but it reduces IOP primarily by stimulating uveoscleral outflow. The PGD2 analogue BW245C is unique in that it is the only PG that decreases aqueous flow. Mechanistic studies in humans have been performed with PGF2 alpha -IE, unoprostone, PhXA34 and latanoprost. In two clinical studies with latanoprost, a significant increase in uveoscleral outflow was found which, as in animals, accounts for most of the IOP reduction. A slight but inconsistent increase in outflow facility may also be involved. The doses tested had minimal effects on the permeability of the blood-aqueous barrier (BAB). In vitro studies of human tissue have been conducted to elucidate the PG effect on outflow facility and uveoscleral outflow. Studies of isolated human anterior segment preparations show that PGE2 increases outflow facility whereas PGF2 alpha has no measurable effect on this parameter. Studies of human ciliary muscle cells in tissue culture indicate that PGs may directly modulate extracellular matrix metabolism, which may be related to the increased uveoscleral drainage. This review summarizes in vitro and in vivo studies of the effects of PGs on aqueous humor dynamics and BAB integrity in humans, cats and monkeys.

Animals↗

PubMed1995

Morphology of ganglion cells in the neotenous tiger salamander retina.

The morphology of retinal ganglion cells in the neotenous tiger salamander (Ambystoma tigrinum) was analyzed with the aid of morphometric techniques to determine the diversity of cell types and to evaluate the widely held notion that this form of Ambystoma has a simple retina, with little variance among its cell morphologies. Single-cell staining was achieved through retrograde labeling with horseradish peroxidase injected around the optic nerve sheath followed by a period of several days before tissue processing; 83 well-labelled cells with axons were studied in detail with light microscopy and a computer-aided reconstruction system. Five different morphological cell classes were devised based on broad morphometric criteria such as the dendritic area of influence; the number, length, and complexity of dendritic branches; and the amount of overlap between neighboring dendrites. These classes included small simple, small complex, medium simple, medium complex, and large cells. In addition, a class of cells with numerous varicosities among the dendrites was separately analyzed. These swellings did not stain for catecholamines. Based on optical determinations of the dendritic sublamination pattern within the inner plexiform layer, presumed On-Off cells are present in all subclasses, whereas On cells predominate in the smaller cell groups. Presumed Off cells are well represented in the large field units, although the small total number of cells in this latter class leads to uncertainty regarding the significance of this observation. The diversity of ganglion cell morphology revealed in the present study argues against the assumption that the neotenous tiger salamander has a simple retina, with a relatively invariant set of ganglion cells. On the contrary, it appears that this aquatic form shows morphological diversity in the retinal ganglion cell population rivaling that reported for other vertebrates, including mammals. A functional role for the different cell classes is briefly considered.

Animals↗

PubMed1995

Effects of brimonidine on aqueous humor dynamics in human eyes.

OBJECTIVE: To evaluate the mechanism by which brimonidine, a selective alpha 2-adrenergic agonist, lowers intraocular pressure (IOP) in humans. SUBJECTS: Twenty-one volunteers with ocular hypertension. METHODS: Brimonidine tartrate (0.2%) was given topically twice daily for 1 week to one eye in a randomized, double-masked study. The fellow eye was similarly treated with brimonidine vehicle. Before (baseline) and after 1 week (day 8) of dosing, IOP, aqueous flow, episcleral venous pressure, and tonographic outflow facility were directly measured. Fluorophotometric outflow facility and uveoscleral outflow were calculated. Brimonidine-treated eyes were compared with vehicle-treated contralateral control eyes and with baseline measurements after 1 week of dosing. RESULTS: Brimonidine significantly (P < .001, Student's two-tailed t test) reduced IOP mean +/- SE of 4.7 +/- 0.7 and 4.2 +/- 0.4 mm Hg compared with the baseline day and with the vehicle-treated contralateral control eyes, respectively. Compared with the baseline day, aqueous flow was reduced by 20% (P = .002) and uveoscleral outflow was increased (P = .04). A slight contralateral decrease in IOP of 1.2 +/- 0.6 mm Hg (P = .05) and in aqueous flow of 12% (P = .05) was noted. No significant difference was seen in the outflow facility values or episcleral venous pressure compared with the baseline day or with the contralateral control eye. CONCLUSIONS: The brimonidine-induced reduction in IOP in humans is associated with a decrease in aqueous flow and an increase in uveoscleral outflow. The decrease in IOP and aqueous flow in the contralateral control eye on day 8 compared with the baseline day suggests a mild contralateral effect.

Administration, Topical↗

PubMed1995

Prostaglandin A2 increases uveoscleral outflow and trabecular outflow facility in the cat.

Prostaglandins (PG) are very effective ocular hypotensive agents. It is generally agreed that these drugs reduce intraocular pressure primarily by increasing uveoscleral outflow. They may also increase trabecular outflow facility though available evidence is less convincing. It has been hypothesized that PGs may increase facility of uveoscleral outflow in addition to their other mechanisms, but this has not yet been tested. To help clarify the ocular hypotensive mechanism of action of a derived PG of the A type, cats were treated twice daily for one week with PGA2 (0.01%) to one eye and vehicle to the other. Measurements were made of aqueous flow and outflow facility with fluorophotometry and of intraocular pressure with pneumatonometry. From these values, uveoscleral outflow was calculated. In addition, total outflow facility, uveoscleral outflow, and uveoscleral outflow facility were determined with invasive methods. PGA2 significantly reduced IOP by a mean of at least 4.7 mmHg in all experiments with all P-values less than 0.01. Compared with contralateral vehicle-treated control eyes, uveoscleral outflow in the treated eye was significantly (P < 0.05) increased by at least 50% using two different methods of measurement. Compared with baseline day, PGA2 significantly (P < or = 0.05) increased aqueous flow by 1.8 microliters min-1, fluorophotometric outflow facility by 0.36 microliter min-1 mmHg-1 and fluorophotometric uveoscleral outflow by 2.0 microliters min-1. Total outflow facility was not significantly different comparing treated with contralateral control eyes. Facility of uveoscleral outflow was < or = 0.02 microliters min-1 mmHg-1 for both control and treated eyes. It is concluded that PGA2 decreases IOP in cats by increasing uveoscleral outflow and trabecular outflow facility as measured with fluorophotometry. A significant increase in aqueous flow reduces the ocular hypotensive effect.

Animals↗

PubMed1995

Effects of apraclonidine on aqueous humor dynamics in human eyes.

PURPOSE: The mechanism by which apraclonidine, an alpha 2-adrenergic agonist, lowers intraocular pressure (IOP) was evaluated in humans. METHODS: In a randomized, double-masked, placebo-controlled study, 0.5% apraclonidine was given topically twice daily for 1 week to one eye in each of 21 ocular hypertensive volunteers. The other eye was treated similarly with vehicle. Before and after 1 week of treatment, aqueous flow, uveoscleral outflow, fluorophotometric outflow facility, intraocular pressure, tonographic outflow facility, episcleral venous pressure, and outflow pressure were either directly measured or mathematically calculated. Values were compared in treated versus contralateral control eyes and on baseline versus day 8 of treatment. RESULTS: When compared with both contralateral control eyes and baseline day, fluorophotometric outflow facility in the apraclonidine-treated eyes increased by 0.09 to 0.10 microliter/minute/mmHg (P < 0.04), IOP decreased by 3.1 to 5.2 mmHg (P < 0.0001), and outflow pressure decreased by 3.3 to 4.2 mmHg (P < 0.0001). When compared with baseline day only, aqueous flow in the apraclonidine-treated eyes decreased by 0.3 microliter/minute (P < 0.04), and episcleral venous pressure decreased by 1.0 mmHg (P < 0.001). Episcleral venous pressure also decreased in the control eyes compared with baseline day by 1.3 mmHg (P < 0.001). When compared with contralateral control eyes only, uveoscleral outflow in the apraclonidine-treated eyes decreased by 0.47 microliter/minute (P < 0.03). Tonographic outflow facility showed no change when compared with either contralateral control eyes or baseline values. CONCLUSIONS: The apraclonidine-induced reduction in intraocular pressure was associated with an increase in fluorophotometric outflow facility, decrease in aqueous flow and decrease in episcleral venous pressure compared to baseline. The lack of a significant difference in aqueous flow and episcleral venous pressure between treated and contralateral control eyes may represent a contralateral drug effect.

Adrenergic alpha-Agonists↗

PubMed1993

Effects of PhXA41, a new prostaglandin F2 alpha analog, on aqueous humor dynamics in human eyes.

PURPOSE: PhXA41, a new phenyl-substituted analog of a prostaglandin F2 alpha (PGF2 alpha) prodrug (13,14-dihydro-17-phenyl-18,19,20-trinor-prostaglandin F2 alpha-1-isopropyl ester), is an effective ocular hypotensive agent in patients with glaucoma. To understand its mechanism of action, various components of aqueous humor dynamics were examined after topical application to human eyes. METHODS: In a randomized, double-masked, placebo-controlled study, PhXA41 (0.006%) was given topically twice daily for 1 week to one eye each of 22 volunteers with normotension or ocular hypertension. The other eye was similarly treated with vehicle. Intraocular pressure (IOP) was measured by pneumatonometry and tonographic outflow facility by pneumatonography. Aqueous flow and outflow facility were determined either directly or indirectly by a fluorophotometric technique, and uveoscleral outflow was calculated secondarily. Comparison of values obtained in treated versus contralateral control eyes and on baseline versus day 8 of treatment were made. RESULTS: Compared with baseline measurements, PhXA41 significantly (P < 0.001) reduced IOP by 5.5 +/- 0.6 mmHg (mean +/- standard error of the mean) as measured 3 hours after the last dose on the eighth day of treatment. Aqueous flow, tonographic outflow facility, and fluorophotometric outflow facility were not changed by PhXA41. However, uveoscleral outflow was significantly greater in the PhXA41-treated eyes (0.87 +/- 0.22 microliter/minute) compared with either the contralateral vehicle-treated eyes (0.14 +/- 0.30; P < 0.02) or baseline measurements (0.39 +/- 0.20 microliter/minute; P < 0.05). CONCLUSIONS: PhXA41 decreases IOP in humans by increasing uveoscleral outflow without significantly affecting other parameters of aqueous humor dynamics.

Adult↗

PubMed1990

Extravascular albumin concentration of the uvea.

The hypothesis that uveal vessels absorb fluid was tested by measuring the albumin in extravascular uveal tissues and in plasma. From these results the effective albumin concentration was calculated in both rabbits and monkeys. Three separate methods were used to measure uveal albumin, and the results of these were compared. In method 1, the intravenous fluorescein isothiocyanate (FITC)-albumin concentration found in the uvea 5 min after injection (intravascular tracer) was subtracted from that found 2 hr after injection (intravascular plus extravascular tracer) to determine the extravascular albumin concentration. In method 2, intravenous FITC-albumin was followed by vascular washout after a 2-hr equilibration period to determine extravascular uveal albumin. In method 3, the endogenous extravascular albumin concentration of uveal tissues was measured with an enzyme-linked immunosorbent assay (ELISA) after vascular washout. The effective albumin concentration was determined by dividing the data in methods 1, 2, and 3 by the extravascular albumin space volume. The effective albumin concentration in monkey (as percentage of plasma) was, for methods 1, 2, and 3: iris 2, 3, and 4%; pars plicata 14, 12, and 7%; pars plana 2, 10, and 12%; and choroid 2, 12, and 10%, respectively. In rabbit, the extravascular albumin concentrations were: iris 10, 21, and 7%; pars plicata 69, 26, and 39%; pars plana 41, 46, and 10%; and choroid 88, 30, and 26%, respectively. These findings are lower than previously reported in rabbits, yet are consistent with previous estimates in monkeys. These results support the hypothesis that uveal vessels are capable of fluid absorption, since a large colloid osmotic gradient exists across the vessel wall.

Albumins↗

PubMed1989

Hydrostatic pressure of the suprachoroidal space.

The hydrostatic pressure of the suprachoroidal space was measured in 18 cynomolgus monkey eyes by one of two methods: (1) direct cannulation, or (2) silicone sponge implantation. The intraocular pressure (IOP) and suprachoroidal pressure were monitored simultaneously with the IOP being held at various levels between 5 and 60 mm Hg. In eyes with direct cannulation, at an IOP of 15 mm Hg, the pressure in the anterior suprachoroidal (supraciliary) space was 0.8 +/- 0.2 mm Hg (n = 6, mean +/- SE) below the IOP, but the posterior suprachoroidal pressure was 3.7 +/- 0.4 mm Hg (n = 8) below the IOP. The suprachoroidal pressure in eyes with silicone sponge implant was 4.7 +/- 0.6 (n = 7) mm Hg below the IOP. A change in IOP produced a corresponding change in the supraciliary space pressure. However, the pressure difference between the anterior chamber and the posterior suprachoroidal space increased at higher IOP. This pressure differential is the driving force for uveoscleral outflow.

Animals↗

PubMed1987

Uveoscleral outflow using different-sized fluorescent tracers in normal and inflamed eyes.

Sodium fluorescein and fluorescinated dextrans (FD) of selected molecular weights were combined and perfused into the anterior chamber of normal and inflamed eyes of cynomolgus monkeys. The eyes were dissected into iris, anterior and posterior uvea, anterior and posterior sclera, retina and intraocular fluids (excluding aqueous). Each tissue was homogenized and centrifuged and the supernatant was run through a gel-filtration column to separate the fluorescent tracers. Each of the resultant peaks was quantitated and facility of uveoscleral outflow was determined. In control eyes the calculated facility of uveoscleral outflow was very similar with all tracers (from 0.047-to 0.052 microliter min-1 mmHg-1) and each tracer was found in highest concentration in the anterior sclera and anterior uvea. In inflamed eyes the calculated facility of uveoscleral outflow increased two- to five-fold with each tracer (0.12-; 0.17-; 0.29-; and 0.24 microliter min-1 mmHg-1 with fluorescein, and the fluorescinated dextrans of MWs 4000, 40,000 and 150,000, respectively). Each tracer was found in the anterior sclera and uvea in inflamed eyes whereas the posterior sclera and uvea contained predominantly the higher molecular-weight tracers (MWs 40,000 and 150,000). It is concluded that iridocyclitis causes an increase in uveoscleral outflow by increasing the permeability of the anterior uvea to all tracers and fluid. Small tracers may then diffuse into uveal blood vessels or across the sclera, yielding lower values for uveoscleral outflow. Of the four tracers studied, the optimal tracer size for studying uveoscleral outflow in either normal or inflamed eyes is MW 40,000.

Animals↗

PubMed1987

Uveoscleral outflow: diffusion or flow?

Shallow peripheral ciliochoroidal detachments with 10(-4) M fluorescein isothiocyanate dextran 70 were created in cynomolgus monkey eyes. Anterior chamber fluorophotometric readings were taken for 6 hr. From the anterior chamber fluorescence values, the rate of tracer movement from the supraciliary space into the anterior chamber was calculated. The rate of movement was 0.003 microliter/min, expressed in equivalent volumes of tracer solution. This value is more than 200 times lower than the rate of tracer movement from the anterior chamber to the supraciliary space. It is concluded that tracer movement from the anterior chamber to the supraciliary space (uveoscleral route) results from fluid flow rather than diffusion.

Animals↗

PubMed1987

Aqueous humor dynamics in experimental iridocyclitis.

Ocular inflammation was induced by intravitreal bovine serum albumin (BSA) injection in one eye of each of six cynomolgus monkeys. The fellow eyes were injected with sterile saline alone. The intraocular pressure decreased by 12.2 +/- 1.3 mmHg (mean +/- SE) 2 days after BSA injection and 4.0 +/- 1.1 mmHg after saline injection. Aqueous flow and uveoscleral outflow were determined with fluorescein isothiocyanate (FITC) dextran 70. Aqueous flow in inflamed eyes averaged 0.32 +/- 0.04 ul/min, less than half the rate of control eyes (0.77 +/- 0.08 ul/min, P = 0.01). The facility of uveoscleral outflow in inflamed eyes was four times that of control eyes (0.2 +/- 0.03 vs 0.05 +/- 0.01 ul/min/mmHg, respectively, P = 0.009). Fluorescence microscopic examination revealed intense fluorescence of the edematous ciliary body muscle and of the suprachoroidal space extending to the posterior pole. These findings indicate that BSA-induced ocular inflammation causes a simultaneous reduction in aqueous humor flow and an increase in uveoscleral outflow, resulting in ocular hypotony.

Animals↗

PubMed1987

Functional recovery of retinal pigment epithelial damage in experimental retinal detachment.

The integrity of the RPE barrier function in retinal detachment was studied in vitro. The retinal pigment epithelium (RPE)-choroid tissue was isolated from cynomolgus monkey eyes with acute (less than 1 hr), subacute (1-2 weeks), and chronic (8-20 months) retinal detachments, and clamped between Ussing-type chambers. Electrical characteristics and choroid-to-retina permeability to carboxyfluorescein were determined. In the HEPES-buffered bathing solution, transepithelial potential difference and resistance in eyes with acute retinal detachments (0.2 mV and 134 ohm-cm2, respectively) were significantly lower than subacute (7.9 and 350) and chronic (10.4 and 348) retinal detachments. Furthermore, the permeability was increased five-fold in acute retinal detachments with respect to subacute and chronic retinal detachments, indicating a breakdown of the RPE barrier in acute retinal detachment. No statistical difference was found between subacute and chronic retinal detachments. In this animal model, RPE barrier function is destroyed at the onset of retinal detachment, but recovers in a week or two, and is maintained in the chronic stage. Histological examination revealed that RPE recovery was accomplished by RPE proliferation and hyperplasia.

Animals↗

PubMed1985

Experimental retinal detachment. VIII. Retinochoroidal horseradish peroxidase diffusion across the blood-retinal barrier.

Unilateral rhegmatogenous retinal detachments in 13 cynomolgus monkeys were studied with horseradish peroxidase (HRP). When injected subretinally in six eyes, HRP did not diffuse anteriorly into the sensory retina and penetrated posteriorly through the zonulae occludentes of the retinal pigment epithelium (RPE) in only two eyes. In seven eyes, tracer was detected after intravitreal HRP injection throughout the sensory retina, the basal lamina of retinal blood vessels, and the subretinal space, but did not penetrate through the RPE. In 13 control eyes (with vitrectomy), intravitreal HRP penetrated the sensory retina and the basal lamina surrounding inner retinal blood vessels. These results confirm that the zonulae occludentes of the RPE and retinal blood vessels remain intact in most eyes after rhegmatogenous retinal detachment. Furthermore, the HRP staining patterns suggest a posteriorly directed movement of fluid across the RPE and possible fluid absorption by retinal blood vessels.

Animals↗

PubMed1985

Experimental retinal detachment. IX. Aqueous, vitreous, and subretinal protein concentrations.

Unilateral rhegmatogenous retinal detachments were created in seven cynomolgus monkeys. Six months later, aqueous, vitreous, and subretinal fluid protein concentrations were measured. In fellow eyes with vitrectomy alone, mean aqueous and vitreous protein concentrations were 0.28 and 0.23 mg/mL, respectively. In eyes with retinal detachments, mean aqueous, vitreous, and subretinal protein levels were 1.46, 2.66, and 4.74 mg/mL, respectively. Eyes with a large retinal hole (greater than or equal to 1 disc diameter) had a subretinal fluid-vitreous protein concentration ratio of 1.1, indicating free diffusional exchange between the vitreous and subretinal space. In eyes with a small retinal hole (less than or equal to 1/4 disc diameter), the corresponding ratio was 4.0. These findings are consistent with the hypothesis that fluid moves from the vitreous cavity through the retinal hole into the subretinal space, preventing back diffusion of protein from the subretinal space into the vitreous, and allowing accumulation of protein in the subretinal space.

Animals↗

PubMed1985

Uveoscleral outflow following cyclodialysis in the monkey eye using a fluorescent tracer.

Cyclodialysis was performed in one eye of each of eight cynomolgus monkeys. Two days later, the intraocular pressure was 1.6 +/- 0.7 mmHg in eyes with cyclodialysis and 12.0 +/- 0.7 mmHg in fellow control eyes. 10(-4) M fluorescein-isothiocyanate dextran (70,000 molecular weight) was perfused into the anterior chamber of each eye for 30 min. The eyes were enucleated and dissected into sclera, choroid, retina, iris, and ocular fluid. Samples were homogenized and centrifuged, and the fluorescence of the supernatant was measured. Expressed as equivalent volumes of aqueous, the rate of anterior chamber movement of tracer via uveoscleral pathways was 1.40 +/- 0.17 microliter/min in cyclodialysis eyes and 0.34 +/- 0.10 microliter/min in control eyes. Cyclodialysis results in a fourfold increase in uveoscleral outflow, contributing to the observed hypotony.

Animals↗

PubMed1985

Effect of intraocular pressure on uveoscleral outflow following cyclodialysis in the monkey eye.

Cyclodialysis was performed in both eyes of five cynomolgus monkeys. Two days later the intraocular pressure (IOP) had fallen from 17.7 +/- 0.8 to 7.1 +/- 1.4 mm Hg (P less than 0.001). At that time, both eyes were perfused for 30 min with fluorescein-isothiocyanate (FITC) dextran (MW 70,000), one at 35 mm Hg and the other at 4 mm Hg. Four pairs of control eyes (without cyclodialysis) were perfused in the same manner. At 4 mm Hg, uveoscleral outflow was 0.02 +/- 0.02 microliter/min in control eyes and 0.05 +/- 0.04 microliter/min in eyes following cyclodialysis. However, at 35 mm Hg, uveoscleral outflow in eyes with cyclodialysis increased to 2.13 +/- 0.47 microliters/min compared to 0.32 +/- 0.10 microliter/min in control eyes. Thus the "facility" of uveoscleral outflow in control eyes is 0.01 microliter/min/mm Hg and in eyes following cyclodialysis is 0.07 microliter/min/mm Hg. It is concluded that cyclodialysis results in a pressure-dependent increase in uveoscleral outflow.

Animals↗

PubMed1984

Experimental retinal detachment. VII. Intravenous horseradish peroxidase diffusion across the blood-retinal barrier.

Intravenous horseradish peroxidase (HRP) was administered to cynomolgus monkeys to study chorioretinal diffusion in eyes with retinal detachment. In control eyes, HRP was contained within the choriocapillaris and did not penetrate beyond Bruch's membrane. In addition, HRP was confined within blood vessels of the sensory retina. In detached eyes, HRP diffused out of the choriocapillaris and through the intercellular spaces of the retinal pigment epithelium (RPE), where it was blocked by zonulae occludentes. Occasionally HRP was found within pinocytotic vesicles of the RPE. It was also confined within retinal blood vessels by their endothelial cells. It is concluded that the blood-retinal barrier remains intact to HRP following long-term rhegmatogenous retinal detachment. However, a slight alteration exists at the choriocapillaris in detached eyes.

Animals↗