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PubMed1984

[A new function of the non-pigmented epithelium of ciliary processes in the formation of aqueous humor].

The invagination of the optic vesicle has, as one of its consequences, the apposition of the apices of the nonpigmented and pigmented epithelia of the ciliary processes of the eye. There are well developed intercellular ciliary "channels" formed at the apices of these cells. Embryologically the ciliary epithelia are homologous to the epithelia of the choroid plexus, a characteristically differentiated ependyma. These epithelial cells have a polarity. For example, the supranuclear region of the nonpigmented epithelia has Golgi apparatus. While stimulation of the epithelia of the choroid plexus by beta adrenergics or cholera toxin increases the rate of production of cerebrospinal fluid, similar stimulation of the adenylate complex within the ciliary epithelia decreases aqueous humor production. When the secretory function of the nonpigmented epithelial cell is activated, fluid is probably reabsorbed from the posterior chamber and secreted apically into the intercellular ciliary channels, in accord with cell polarity, thereby reducing net aqueous inflow. The fluid may enter the ciliary stroma thereafter and thus may become part of what may be called "uveal scleral" flow, or in this instance, uveal flow. The anatomy, physiology, and chemistry fit this hypothesis and form the basis for new investigations of a two-way transport across the ciliary epithelia.

Animals↗
PubMed1996

Transscleral flow of aqueous humor: an in vitro experiment.

BACKGROUND AND OBJECTIVE: The minimal scleral flap thickness to ensure transscleral flow following a trabeculectomy has never been determined. The present study was designed to determine, in vitro, the critical scleral flap thickness that allows transscleral flow. MATERIALS AND METHODS: The apparatus consisted of two horizontal glass chambers (A and B) connected to each other by a customized scleral disc holder. High-pressure chamber A (at 25 mm Hg) was filled with sodium pertechnetate (99mTc) labeled normal saline and low-pressure chamber B (at 5 mm Hg) with normal saline. Transscleral flow of labeled normal saline from high-pressure chamber A via varying thickness scleral discs to low-pressure chamber B was observed over 16 hours using a gamma camera. Computer analysis was performed on the obtained images. RESULTS: Transscleral flow of labeled saline was observed only with scleral discs 0.5 mm thick or less. CONCLUSIONS: If the findings hold true for the in vivo situation, aqueous humor may reach the subconjunctival space following trabeculectomy via the transscleral route, provided scleral flap thickness is less than 0.5 mm. In addition, normal uveoscleral aqueous outflow may occur across sclera less than 0.5 mm thick, e.g., posterior to extraocular muscle insertions.

Aqueous Humor↗
PubMed1993

Levels of vancomycin in aqueous humor after topical eye drops administration.

Vancomycin is an antibiotic which is especially active against Gram positive bacteria. At present, numerous infections of the anterior segment of the eye are caused by the Staphilococcus aureus and epidermis. Strains which are resistant to methicilin are more and more frequent and for this reason Vancomycin is becoming the antibiotic of choice to combat these infections since no resistance of the Staphilococcus to it has been demonstrated. The authors evaluated the levels of Vancomycin in aqueous humor after the administration of topical eye-drops. For the first two hours after the last administration, levels of 0.52 micrograms/ml were detected. These inhibit the growth of the majority of bacteria sensitive to Vancomycin. Between two and four hours, the levels decreased to 0.15 micrograms/ml; these are therapeutic levels for a large number of Gram positive bacteria. From four hours after the last administration, these levels are undetectable. Due to the success of its penetration, topical administration of Vancomycin should be considered as a therapeutic modality against infections by gram positive bacteria of the anterior segment. The ideal guideline for administration would be one drop every two hours, especially if the infection is severe. In this way, subconjunctival injection could be avoided.

Anterior Eye Segment↗
PubMed1994

Trabecular outflow facility and formation rate of aqueous humor during intravenous cocaine or lidocaine in rabbits.

This study examined the effect of cocaine and lidocaine on intraocular pressure (IOP), fluid formation, outflow facility, and compliance. Fourteen New Zealand White rabbits were anesthetized with halothane (0.8-1.0% inspired concentration) in nitrous oxide (2 L/min) and oxygen (1 L/min). Pancuronium was given intravenously (i.v.) to produce neuromuscular block, and the lungs were mechanically ventilated through a tracheal tube. In one group (n = 8) cocaine 0.5 mg/kg followed by 1.0 microgram.kg-1.min-1 i.v. was added to halothane/nitrous oxide/oxygen anesthesia. In the second group (n = 6) lidocaine 0.5 mg/kg followed by 1.0 microgram.kg-1.min-1 i.v. was added to halothane/nitrous oxide/oxygen anesthesia. In both groups a series of intraocular infusions was made via a 30-gauge needle in the anterior chamber and IOP, the rate of aqueous humor formation, trabecular outflow facility, and intraocular compliance were determined. In Group I, IOP was 15.0 +/- 6.3 mmHg prior to and 14.5 +/- 7.1 mm Hg after cocaine. The rate of anterior chamber aqueous formation was 3.79 +/- 1.25 microL/min and trabecular outflow facility was 0.141 +/- 0.090 microL.min-1.mm Hg-1. In Group 2, IOP was 14.4 +/- 4.8 mm Hg prior to lidocaine and IOP decreased (P < 0.05 compared to precocaine in Group 1 and prelidocaine in Group 2) to 11.9 +/- 6.8 mm Hg after lidocaine. The rate of anterior chamber aqueous formation was 2.59 +/- 0.86 microL/min and trabecular outflow facility decreased (P < 0.05 compared to Group 1) to 0.077 +/- 0.040 microL.min-1.mm Hg-1. Intraocular compliance during cocaine, 36 +/- 12 nL/mm Hg, was similar to that during lidocaine, 33 +/- 14 nL/mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Intravenous↗
PubMed1989

Morphologic features of the aqueous humor drainage pathways in horses.

The iridocorneal angle of the horse was anteriorly lined by a pectinate ligament, consisting of several layers of vertically oriented collagenous beams, that were interrupted by a network of extracellular spaces. The anterior chamber angle consisted mostly of a large uveal trabecular meshwork that was composed of widely-spaced, thick trabeculae. These trabeculae were attached in part posteriorly to extensions of the ciliary body musculature and anteriorly inserted into the prominent pectinate ligament. The corneoscleral trabecular meshwork was shaped hemiobovately and formed the external boundary of the iridocorneal angle. The extracellular spaces were smaller and more evenly spaced than those in the uveal trabecular meshwork. Uveal and corneoscleral trabecular meshwork beams were mostly composed of cores of collagen and elastin surrounded by several layers of basement membrane-like material and, in turn, were entirely enveloped by trabecular cells. An anterior narrow zone of broad corneoscleral trabeculae was composed of elastin-collagen cores surrounded by circular bundles of long-spacing collagen. The angular aqueous plexus was extensive, forming much of the external border of the outer corneoscleral trabecular meshwork. A dense zone was associated with the angular aqueous plexus, completely encompassing these aqueous outflow vessels. Posteriorly, the iridocorneal angle was confluent with a well-defined band of trabeculae that was situated between the ciliary body musculature and subjacent sclera and extended posteriorly to the anterior-most region of the choroid where these trabeculae tapered and ended. This region is referred to as the supraciliary trabecular meshwork and indicates a potentially extensive route for outflow of aqueous humor in the equine eye.

Animals↗
PubMed1997

Inhibition of glutamate uptake causes an acute increase in aqueous humor protein.

Inhibition of glutamate transport has been shown to increase paracellular permeability of epithelial cell monolayers in vitro. To determine if blocking glutamate transport would affect tissue permeability in vivo, D-aspartate (D-Asp; 300 nmol 30 microliters-1) (a non-toxic competitive inhibitor of glutamate transport) or a placebo was injected into the anterior chambers of the fellow eyes of 15 adult rabbits. [14C]-L-glucose and/or [125I]-rabbit albumin were included in the injection vehicle as aqueous humor (AH) outflow markers. The specific inhibition of glutamate uptake by D-Asp was indicated by a 15% increase in AH glutamate (174 +/- 9 nmol ml-1 to 205 +/- 13 nmol ml-1; P = 0.03) at 1-1.5 hr post injection. Also, the efflux of [14C]-L-glucose and [125I]-rabbit albumin from the AH of D-Asp injected eyes was increased 22% over the placebo-injected control eyes (P < or = 0.02). Concomitantly, the total protein concentration in the AH from D-Asp injected eyes (517 +/- 35 micrograms ml-1) was 19% greater (P < 0.02) than the protein concentration in AH from placebo-injected control eyes (420 +/- 36 micrograms ml-1). In additional studies, an irreversible inhibitor of glutamate transport, threo-beta-hydroxyaspartate (THA; 30 nmol 30 microliters-1), was shown to increase the efflux of [14C]-L-glucose (22%; P < 0.05) from the anterior chamber and increase AH protein concentrations by 29% (484 +/- 112 micrograms ml-1 in control AH versus 686 +/- 117 micrograms ml-1 in THA AH, P = 0.08) at 1 hr post intracameral injection. SDS-PAGE analysis of the AH associated the protein increase in the D-Asp and THA injected eyes but not placebo-injected control eyes with a detectable increase in a 66 kDa protein (aligns with serum albumin) and several lower molecular weight (23-35 kDa) AH proteins. The results found suggest that inhibition of glutamate transport from the AH acutely increases intraocular epithelial/endothelial paracellular permeability.

Alanine↗
PubMed1991

Selective alpha 2-adrenergic agonists B-HT 920 and UK14304-18. Effects on aqueous humor dynamics in monkeys.

Selective alpha 2-adrenergic agonists UK14304-18 and B-HT 920 were evaluated in the eyes of cynomolgus monkeys. In normal monkeys, unilateral topical application of 0.3%, 0.5%, or 1% UK14304-18 or B-HT 920 reduced (P less than .05) intraocular pressure bilaterally up to 9.9 +/- 1.2 mm Hg (mean +/- SEM) and 8.4 +/- 1.4 mm Hg in treated and contralateral eyes, respectively. Five-day twice-daily 0.5% UK14304-18 administration reduced (P less than .05) intraocular pressure up to 49% in eight glaucomatous monkeys. In eight normal monkeys, 0.5% B-HT 920 and 0.5% UK14304-18 produced no alterations in outflow facility. Following unilateral application of 0.5% B-HT 920 or 0.5% UK14304-18, fluorophotometrically measured aqueous humor production was reduced (P less than .05) bilaterally up to 67% compared with baseline values. Also, 0.5% UK14304-18 reduced (P less than .025) systolic and diastolic blood pressure. UK14304-18 and B-HT 920 seem to reduce intraocular pressure by decreasing aqueous production. They are potential new agents for the treatment of glaucoma.

Administration, Topical↗
PubMed2006

Evaluation of concentration of voriconazole in aqueous humor after topical and oral administration in horses.

OBJECTIVE: To determine penetration of topically and orally administered voriconazole into ocular tissues and evaluate concentrations of the drug in blood and signs of toxicosis after topical application in horses. ANIMALS: 11 healthy adult horses. PROCEDURE: Each eye in 6 horses was treated with a single concentration (0.5%, 1.0%, or 3.0%) of a topically administered voriconazole solution every 4 hours for 7 doses. Anterior chamber paracentesis was performed and plasma samples were collected after application of the final dose. Voriconazole concentrations in aqueous humor (AH) and plasma were measured via high-performance liquid chromatography. Five horses received a single orally administered dose of voriconazole (4 mg/kg); anterior chamber paracentesis was performed, and voriconazole concentrations in AH were measured. RESULTS: Mean +/- SD voriconazole concentrations in AH after topical administration of 0.5%, 1.0%, and 3.0% solutions (n = 4 eyes for each concentration) were 1.43 +/- 0.37 microg/mL, 2.35 +/- 0.78 microg/mL, and 2.40 +/- 0.29 microg/mL, respectively. The 1.0% and 3.0% solutions resulted in significantly higher AH concentrations than the 0.5% solution, and only the 3.0% solution induced signs of ocular toxicosis. Voriconazole was detected in the plasma for 1 hour after the final topically administered dose of all solutions. Mean +/- SD voriconazole concentration in AH after a single orally administered dose was 0.86 +/- 0.22 microg/mL. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that voriconazole effectively penetrated the cornea in clinically normal eyes and reached detectable concentrations in the AH after topical administration. The drug also penetrated noninflamed equine eyes after oral administration. Low plasma concentrations of voriconazole were detected after topical administration.

Administration, Oral↗
PubMed1983

Radial keratotomy. Effect on cornea and aqueous humor physiology in the rabbit.

Radial keratotomy may cause anatomical damage to the rabbit corneal endothelium. To determine if physiological and functional alterations occur, radial keratotomy was performed on rabbit corneas using eight incisions with sparing of a 3.5-mm central pupillary area. Cornea endothelial membrane permeabilities were determined at various times up to ten weeks following the procedure using simultaneous flux determinations of tritiated inulin and dextran labeled with radioactive carbon on isolated corneas. At all times after radial keratotomy, there was no probable physiologically important change in corneal endothelial permeability to either of the labeled compounds. Fluorophotometry performed in a second group of animals at varying intervals following radial keratotomy showed no probable physiologically important change in endothelial fluorescein permeability. Aqueous humor turnover rate was reduced 16% and 29% at one week and nine to ten weeks, respectively, following radial keratotomy.

Animals↗
PubMed2002

Soluble Fas ligand and transforming growth factor beta2 in the aqueous humor of patients with endothelial immune reactions after penetrating keratoplasty.

BACKGROUND: Excellent long-term prognosis of penetrating corneal grafts has been explained by the immunological privilege of the cornea and the anterior chamber. In animal models the secretion of transforming growth factor beta(2) (TGF-beta(2)) into the anterior chamber and the expression of the Fas ligand on corneal endothelial cells were identified as important for the integrity of the immunological privilege. OBJECTIVE: To determine the TGF-beta(2) and soluble Fas ligand (sFasL) levels in the aqueous humor of patients after penetrating keratoplasty (PK) who have and who do not have immune reactions. METHODS: Anterior chamber puncture was performed in 13 patients who had a cataract without PK (group 1), in 31 patients after PK who did not have immune reactions (group 2), and in 12 patients after PK newly diagnosed as having endothelial immune reactions (group 3). Total TGF-beta(2) and sFasL were determined via enzyme-linked immunosorbent assay. RESULTS: Transforming growth factor beta(2) was detected in all patients, irrespective of the underlying condition; there was no difference in TGF-beta(2) levels between the different groups (P =.89, analysis of variance). None of the patients in group 1, 11 of 31 patients in group 2, and 8 of 12 patients in group 3 had detectable sFasL concentrations (P =.002, chi(2) test). Soluble Fas ligand averaged (mean [SD]) 20.8 (31.1) pg/mL in group 2, and 38.1 (33.2) pg/mL (P<.01, analysis of variance) in group 3. CONCLUSIONS: It appears that total TGF-beta(2) is maintained at high steady-state levels, while the level of sFasL is up-regulated in patients who underwent PK, particularily in the advent of graft rejection.

Aged↗
PubMedDate not supplied

Microbiologic analysis of aqueous humor in phacoemulsification.

PURPOSE: This study was designed as a microbiologic survey of the fluids aspirated from the anterior chamber at the end of cataract extraction performed by phacoemulsification, and to correlate the contamination rate of the anterior chamber to the surgical technique used. METHODS: One hundred and one consecutive patients (126 eyes) who underwent cataract extraction by phacoemulsification and posterior chamber intraocular lens implantation were included in the study. Microscopical examination, culture, and determination of the number of colonies were carried out on the bacteria and fungi in the anterior chamber fluids aspirated at the end of surgery, before final suture placement. RESULTS: Anterior chamber fluids yielded positive cultures in nine specimens (8.14%), six of which were identified as coagulase-negative staphylococci. Quantification disclosed colony counts ranging between 2-10 and 10-40 per mL. CONCLUSIONS: Preliminary results in a small population show that the contamination of the aqueous humor is significantly less frequent if the cataract extraction is performed by phacoemulsification.

Adult↗
PubMedDate not supplied

Inhibition of lymphocyte proliferation by aqueous humor.

Antigens introduced into the anterior chamber (AC) of the eye elicit systemic, antigen-specific suppression of delayed hypersensitivity combined with primed cytotoxic T cells and elevated levels of serum antibodies, a unique immune response termed anterior chamber associated immune deviation (ACAID). Among the mechanisms that have been implicated in the induction of this response is the possibility that T cells first recognize antigen within the AC, where-upon they then escape to initiate the induction of systemic suppression. Because this possibility implies that T-cell recognition of antigen could occur in the aqueous humor (AqH) that normally fills the AC, we tested the effects of freshly obtained AqH on lymphocyte proliferative responses in vitro. The results indicate that AqH from mice and rabbits profoundly inhibits (1) T-lymphocyte proliferation to antigens, (2) T- and B-lymphocyte responses to polyclonal mitogens, and (3) growth-factor-driven lymphocyte proliferation. The antiproliferative activity of AqH was also effective on some, but not all, neoplastic cells. The activity was shown to be neither species specific nor directly cytotoxic to cells. The activity was distinct from the growth inhibitory effects of normal mouse serum. We conclude that AqH contains a soluble factor(s) that is a potent inhibitor of cell proliferation. The potential role(s) of this activity in ocular wound healing and in intraocular immune responses are discussed.

Animals↗
PubMed2004

Topical glucocorticoid therapy directly induces up-regulation of functional CXCR4 on primed T lymphocytes in the aqueous humor of patients with uveitis.

Overexpression of the constitutive chemokine receptor CXCR4 has been shown to contribute to the accumulation of leukocytes at sites of chronic inflammation. Glucocorticoids are widely used to treat inflammatory disorders such as uveitis to considerable effect, yet paradoxically have been reported to increase CXCR4 expression in vitro. We show here that ocular lymphocytes isolated from patients with uveitis who had been treated with topical glucocorticoids expressed highly elevated levels of CXCR4. The up-regulation of CXCR4 could be reproduced in vitro by culture of CD4(+) T cells with aqueous humor (AqH), indicating a role for the ocular microenvironment rather than preferential recruitment of CXCR4(+) cells. Untreated uveitis and noninflammatory AqH up-regulated CXCR4 to a limited extent; this was dependent on TGF-beta2. However, the highest levels of CXCR4 both in vivo and in vitro were found in the glucocorticoid-treated patients. Glucocorticoids appeared to be directly responsible for the induction of CXCR4 in treated patients, as the glucocorticoid receptor antagonist RU38486 inhibited the in vitro up-regulation by AqH from these patients. Dexamethasone selectively up-regulated CXCR4 in vitro, but not any of a wide range of other chemokine receptors. CXCL12, the ligand for CXCR4, was present in AqH under noninflammatory conditions, but the levels were low in untreated uveitis and undetectable in treated uveitis AqH. The importance of these results for the treatment of HIV patients with glucocorticoids is discussed as well as a role for glucocorticoid-induced CXCR4 up-regulation and CXCL12 down-regulation in controlling the migration of lymphocyte populations, resulting in resolution of inflammation.

Administration, Topical↗
PubMed1986

ATPases of ciliary epithelium: cellular and subcellular distribution and probable role in secretion of aqueous humor.

The distribution of ion-stimulated ATPases of the ciliary epithelium has been examined in tissues from bovine and rabbit eyes. In homogenates of tissues from both species, both Na,K- and anion-stimulated enzyme activities were found, but no K,H-stimulated activity was detected. The anion ATPase had a broad specificity for a number of anions, and was strongly inhibited by thiocyanate. Following separation of pigmented (outer) and non-pigmented (inner) layers of the bovine ciliary epithelium and isolation of the two cell types on density gradients, higher activities of both Na,K- and anion ATPases were found in the non-pigmented cells. Subcellular fractionation of a mixed population of cells showed that the anion ATPase was almost exclusively associated with a mitochondrial fraction, rather than with the plasma-membrane fraction containing the Na,K-ATPase. These results confirm histochemical studies of the distribution of Na,K-ATPase in the ciliary epithelium and support the concept that the inner, non-pigmented cell layer is chiefly responsible for the active transport of ions into the posterior chamber. It is concluded that this transepithelial transport can be driven only by the energy derived via the Na,K-ATPase, and that any subsequent anion or proton transport in the formation of aqueous humor is driven by the sodium gradient through exchange mechanisms.

Adenosine Triphosphatases↗
PubMed1991

Dynamic sodium chemical shift imaging for the study of aqueous humor flow.

Ocular images were obtained using sodium chemical shift imaging (CSI) and 1,4,7,10-tetraazacyclododecane-N,N'N",N"'-tetramethylenephospho nate thulium (III) [Tm(DOTP)5-], a paramagnetic chemical shift reagent. After injecting the shift reagent into the anterior chamber of rabbits, serial imaging was done, monitoring the change in chemical shift with time. Sodium CSI produced images of the eye in three dimensions, quantitatively depicting the spatial and temporal changes in the concentration of a paramagnetic tracer substance. The Tm(DOTP)5- is eliminated from the anterior chamber by first-order kinetics with a half-life of 49 min. These data suggest that this substance is eliminated from the anterior chamber at the same rate as aqueous humor is replaced. Sodium CSI shows promise as a valuable technique for monitoring fluid dynamics in the living eye.

Animals↗