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Results for “Aqueous Humor”

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PubMed1994

The effect of melatonin on aqueous humor flow in humans during the day.

BACKGROUND: Aqueous humor flow through the anterior chamber of the eye undergoes a circadian cycle. The rate of flow during the day is twice as high as the rate of flow at night. The pineal hormone, melatonin, also undergoes a circadian cycle. Melatonin levels are high at night, whereas aqueous humor flow is low. The authors studied the effect of oral melatonin on aqueous humor flow in humans. METHODS: The effect of melatonin on aqueous humor flow was evaluated in 19 healthy human volunteers in a randomized, masked crossover study with a placebo control. The hormone or placebo was administered orally during the day when endogenous levels of melatonin are low. Aqueous flow was measured by fluorophotometry for 8 hours. RESULTS: The mean rate of flow during melatonin treatment was 2.71 +/- 0.64 microliters/minute (+/- standard deviation). The rate of flow during placebo treatment was 2.80 +/- 0.66 microliters/minute. There is no statistically significant difference between these two rates (P = 0.4). With a sample size of 19, the study has a power of 92% to detect at least a 15% difference in the rate of flow under the two conditions. Measurement of plasma concentration of melatonin in five subjects confirmed that concentrations after oral dosage reached peaks comparable with the normal endogenous nocturnal peaks. CONCLUSIONS: The authors conclude that melatonin concentrations during the day, comparable with plasma concentrations that occur spontaneously during sleep, do not suppress aqueous humor formation. The authors find no support for the idea that plasma melatonin, per se, can suppress aqueous formation or that the circadian rhythm of plasma melatonin is primarily responsible for the circadian rhythm of aqueous humor flow.

Administration, Oral↗

PubMed1984

The effects of carbonic anhydrase inhibitors on aqueous humor chemistry and dynamics.

The effects of topical application of the carbonic anhydrase inhibitor trifluormethazolamide (TFM) on intraocular pressure (IOP), ascorbate and CO2 concentrations in aqueous humor, and aqueous humor flow were studied in rabbits. These effects were compared with those produced by systemic treatment with methazolamide. The decrease in IOP observed after TFM was accompanied by changes in the composition of the aqueous humor. Posterior aqueous ascorbate concentration showed a marked increase (up to 1.7-fold), whereas the anterior aqueous ascorbate did not change significantly. Similar changes were found in rabbits after systemic treatment with methazolamide. A small but statistically significant decrease in the CO2 content of both posterior and anterior aqueous was observed after topical TFM application. Methazolamide yielded a more profound lowering in the CO2 content of the aqueous humor, a reflection of the significant decrease in plasma CO2 content. For topical TFM or systemic methazolamide doses yielding complete inhibition of carbonic anhydrase in the eye, a 55-59% reduction of aqueous flow was calculated from the ascorbate data using the Kinsey and Palm equation. However, a 31-42% reduction in aqueous flow was obtained from the same data using an equation based only on posterior chamber data. The reasons for using only posterior aqueous ascorbate data for calculating the changes in aqueous humor flow are discussed.

Administration, Topical↗

PubMed1999

Effect of aqueous humor on apoptosis of inflammatory cell types.

PURPOSE: To determine whether aqueous humor promotes cell death in cells involved in inflammatory responses. METHODS: Multiple immune cell types, most characteristically involved in inflammatory responses, were incubated for 24, 48, and 72 hours in the presence or absence of 50% aqueous humor. Promotion of cell death was assayed by staining for an early indicator of apoptosis. The percentage of cells undergoing apoptosis was measured by flow cytometry. To identify partially the apoptosis inducing factor, aqueous humor was pretreated with proteinase K to degrade protein. In other experiments, aqueous humor was fractionated by centrifugation on filters capable of separating molecules above and below 10 kDa or 30 kDa kilodaltons in size. RESULTS: Rabbit aqueous humor promoted apoptosis in a wide variety of immune cells, including lymphokine-activated natural killer cells, resting T cells, an activated T-cell line, RAW 264.7 and J774A0.1 monocyte-macrophage cell lines, and neutrophils. As previously shown, aqueous humor did not promote apoptosis of murine corneal endothelial cells. Apoptosis was also not induced in human corneal endothelium, mouse corneal epithelium, or iris/ciliary body cell lines. Instead, aqueous humor partially protected these ocular tissues from starvation-induced cell death. Pretreatment with proteinase K inhibited the apoptosis-inducing activity. Moreover, the apoptosis-inducing activity segregated with the aqueous humor fraction containing molecules less than than 10 kDa in size. CONCLUSIONS: These data show that aqueous humor contains a factor or factors that promote death of cells that participate in inflammatory processes. By contrast, ocular tissues, such as the corneal endothelium and iris/ciliary body, are impervious to aqueous humor-induced cell death. The aqueous humor- borne factor(s) may contribute to the immune privilege of the anterior chamber by purging potential inflammatory cells.

Animals↗

PubMed1998

Suppression of nitric oxide generated by inflammatory macrophages by calcitonin gene-related peptide in aqueous humor.

PURPOSE: Ocular immune privilege is mediated in part by the activity of constitutively produced immunosuppressive cytokines and neuropeptides. Aqueous humor was examined for content of calcitonin gene-related peptide (CGRP), and the potential of CGRP to mediate immunosuppressive activity within aqueous humor was determined. METHODS: The concentration of CGRP in fresh, normal rabbit aqueous humor was assayed by competitive enzyme-linked immunosorbent assay. The ability of CGRP to suppress interferon (IFN)-gamma production by antigen-stimulated, primed lymph node cells was examined by assaying supernatants of stimulated CGRP-treated, primed T-cell cultures for IFN-gamma. The anti-inflammatory activity of aqueous humor and CGRP was assayed by treating IFN-gamma-lipopolysaccharide (LPS)-activated RAW 264.7 cells (macrophages) with aqueous humor, aqueous humor plus anti-CGRP antibody, or CGRP alone. Culture supernatants of the treated macrophages were examined for nitrite by Griess reagent. The production of inducible nitric oxide synthase (NOS2) protein was examined by immunoblotting cell lysates of treated activated macrophages. RESULTS: The constitutive level of CGRP in fresh, normal rabbit aqueous humor was 5+/-1 x 10(-5) M. At its ocular concentration, CGRP did not inhibit IFN-gamma production by stimulated effector T cells, but it suppressed nitric oxide generation by activated macrophages. Neutralization of CGRP in normal rabbit aqueous humor prevented the aqueous humor from suppressing nitric oxide generation by macrophages. Neither CGRP nor aqueous humor suppressed NOS2 protein synthesis in activated inflammatory macrophages. CONCLUSIONS: Calcitonin gene-related peptide is a constitutive neuropeptide in aqueous humor. Through CGRP, aqueous humor suppresses nitric oxide production by activated macrophages. This suppression appears to result from inhibiting NOS2 enzymatic activity, rather than from suppressing NOS2 synthesis. The results imply that the ocular microenvironment has diverse immunoregulatory mechanisms that suppress induction, activation, and mediation of immunogenic inflammation.

Animals↗

PubMed1978

Aqueous humor lactate dehydrogenase in retinoblastoma patients. Clinicopathologic correlations.

Aqueous humor lactate dehydrogenase (LDH) levels were assayed for 23 patients with histologically proved retinoblastoma. The mean aqueous level was 1,886 IU/liter. Twenty-one of these patients had an aqueous humor LDH level above the normal mean. Clinicopathological parameters were determined and evaluated using standard statistical formulas. Only the presence of tumor in the anterior chamber correlated significantly with the aqueous humor LDH level. The following clinical features did not correlate with aqueous humor LDH levels: sex, family history, bilaterality, prior treatment, presentation age, enucleation age, and metastasis. The following pathological features did not correlate with aqueous humor LDH levels: calcification, necrosis, rosettes, inflammation, choroidal or optic nerve invasion, or neovascularization.

Aqueous Humor↗

PubMed2006

Increased levels of pigment epithelium-derived factor in aqueous humor of patients with uveitis.

AIM: To evaluate whether aqueous humor levels of pigment epithelium-derived factor (PEDF) are increased in patients with uveitis METHODS: Aqueous humor levels of PEDF and tumour necrosis factor alpha (TNFalpha) were determined by ELISA in 34 uveitis samples and 9 cataract control samples. RESULTS: Aqueous humor PEDF and TNFalpha levels were significantly higher in patients with uveitis than in controls (mean (SD) 6.4 (0.8) v 1.3 (0.2) microg/ml and 14.7 (3.8) v 4.2 (0.4) pg/ml, respectively; p<0.01). A positive correlation between PEDF and TNFalpha was found in patients with uveitis (r = 0.40, p<0.01). Furthermore, PEDF levels in aqueous humor were increased in proportion to the disease activity of uveitis. CONCLUSION: The results show that aqueous humor levels of PEDF are increased in patients with uveitis. Our observations suggest that aqueous humor levels of PEDF may be increased as a countersystem against inflammation in uveitis.

Adult↗

PubMed1983

Lipid composition of human aqueous humor.

The lipid composition of human aqueous humor was determined in ten samples from patients undergoing cataract surgery. The mean concentration was 16.4 mg/dl for total lipids, 2.5 for phospholipids, 1.1 for free fatty acids, 1.7 for unesterified cholesterol 2.0 for triglycerides, and 9.0 mg/dl for cholesterol esters, respectively. The presence of lipids in aqueous humor suggests that lipids are transported through the human aqueous humor.

Aged↗

PubMed1979

Rhesus monkey aqueous humor composition and a primate ocular perfusate.

The composition of rhesus monkey aqueous humor has been studied in large-volume, pooled samples. Replicate determinations of the concentrations of a number of constituents have been carried out for both aqueous humor and serum from large veins by means of automatic analyzing equipment. Since aqueous humor has been obtained by anterior chamber paracentesis, it is a mixture of anterior and posterior chamber aqueous. When compared to serum, the pooled aqueous contains an excess of chloride, bicarbonate, ascorbate, lactate, uric acid, and several neutral amino acids. Rhesus monkey aqueous humor is deficient in calcium, urea nitrogen, phosphates, glucose, protein, creatinine, iron, bilirubin, cholesterol, triglycerides, a number of serum enzymes, acidic and basic amino acids, and several neutral amino acids. Sodium, potassium, magnesium, and two neutral amino acids (cysteine and valine) are of equal concentration in aqueous humor and serum. Glutathione concentration is very low in both aqueous humor and serum. Pooled rhesus monkey aqueous humor and serum are isosmolar, with measured osmolality being about 303 mOsm. Based upon the chemical analysis, a new solution has been formulated to substitute for primate aqueous humor during anterior ocular perfusion. This new solution causes very little change in the physiologic integrity of the outflow pathways during prolonged, repeated perfusion. In this respect, its effects are very similar to those of pooled rhesus monkey aqueous humor during perfusion of rhesus monkey eyes. In contrast, perfusion of rhesus monkey eyes with glutathione-bicarbonate-Ringer's solution has been shown to cause progressive increase of the total facility. To minimize physiologic alterations during operative procedures, a solution similar to this new one could be formulated for irrigation of the inside of the human eye.

Animals↗

PubMed2005

Penetration of topically applied gatifloxacin 0.3%, moxifloxacin 0.5%, and ciprofloxacin 0.3% into the aqueous humor.

PURPOSE: To investigate the aqueous penetration of 3 commercially available ophthalmic fluoroquinolones. DESIGN: Prospective, double-masked, clinical study. PARTICIPANTS: Fifty-two eyes of 52 patients. INTERVENTION: Fifty-two patients undergoing cataract surgery were given preoperative topical gatifloxacin 0.3% (Zymar), moxifloxacin 0.5% (Vigamox), or ciprofloxacin 0.3% (Ciloxan). The patients were instructed to use their antibiotic drops 4 times a day for 3 days before surgery. On the day of surgery, patients were given their assigned antibiotic every 15 minutes for 3 doses, 1 hour before their procedure. At the time of surgery, 0.1 ml of aqueous fluid was aspirated from the anterior chamber with an air cannula needle attached to a tuberculin syringe. The aspirate was immediately stored at -70 degrees C. MAIN OUTCOME MEASURE: Fluoroquinolone concentrations were determined by reverse-phase high-pressure liquid chromatography assay technique with ultraviolet detection at a wavelength of 275 nm. RESULTS: Mean aqueous concentration of gatifloxacin in 16 eyes was 0.63 microg/ml (standard deviation [SD], 0.30), moxifloxacin in 14 eyes was 1.31 microg/ml (SD, 0.46), and the mean concentration of ciprofloxacin in 22 eyes was 0.15 microg/ml (SD, 0.11). CONCLUSIONS: Both moxifloxacin (P<0.001) and gatifloxacin (P<0.005) penetrated the aqueous humor at significantly higher levels than ciprofloxacin. Moxifloxacin penetrated into the aqueous humor at significantly higher levels than gatifloxacin (P<0.05). The anterior chamber levels of moxifloxacin and gatifloxacin may be due to the difference in antibiotic concentration.

Aged↗

PubMed1993

Substance P inactivation by aqueous humor.

Degradation of substance P was studied in dog and rabbit aqueous humor. Substance P inactivation was followed by the bioassay using the isolated guinea pig ileum. Both rabbit and dog aqueous humor inactivated substance P. Rabbit aqueous humor inactivated the peptide faster than dog aqueous humor. Inactivation of substance P by rabbit aqueous humor was inhibited by diisopropylfluorophosphate while other enzyme inhibitors tested (captopril, phosphoramidon, mersalyl acid and p-chloromercuriphenyl-sulphonate) were practically ineffective or had a partial inhibitory effect. Our results suggest that serine proteases, rather than other peptidases, play a major role in the inactivation of substance P in aqueous humor.

4-Chloromercuribenzenesulfonate↗

PubMed1988

Ocular pharmacokinetics of latamoxef and cefaclor in rabbits. Penetration into aqueous humor.

Penetrations of latamoxef (LMOX) and cefaclor (CCL) into the aqueous humor after intravenous or oral administration were investigated in rabbits. Concentrations of antibiotics in plasma and aqueous humor after administration were determined periodically by microbiological assay. LMOX disappeared from plasma in a monoexponential manner with a half-life of 43 min after intravenous administration at a dose of 50 mg/kg. The maximum concentration of LMOX in aqueous humor (6.4 micrograms/ml) was observed 1 h after administration. When CCL was administered orally at a dose of 50 mg/kg, the maximum concentration of CCL in aqueous humor was 1.00 microgram/ml 1.5 h after administration, whereas the maximum plasma concentration of 19.2 micrograms/ml was observed at 30 min. Pharmacokinetic analysis (simultaneous simulation) of plasma and aqueous humor concentration-time courses was made using the best fitted compartment model examined (modified two-compartment model). Prediction of the concentration of antibiotics in aqueous humor from the plasma concentration profile was also examined using the same compartment model in a separate experiment. The predicted concentration in aqueous humor was proved to coincide reasonably well with the measured concentration.

Administration, Oral↗

PubMed1994

Aqueous humor penetration of ofloxacin given by various routes.

We studied the aqueous humor penetration of ofloxacin after topical, oral, and intravenous administration in 51 consecutive patients undergoing cataract surgery. Aqueous humor concentration (mean +/- SD) was 0.53 +/- 0.35 mg/l when ofloxacin 0.3% eyedrops were instilled topically six times, one drop every three hours, until 90 minutes preoperatively, and 0.63 +/- 0.29 mg/l (P = .45) when two additional instillations were made, one drop every 30 minutes, until 30 minutes before aqueous humor aspiration. Aqueous humor concentration two hours after a single 200-mg oral dose (0.38 +/- 0.15 mg/l) was significantly lower (P = .048) than that 12 hours after the same oral dose (0.58 +/- 0.24 mg/l). Two hours following an intravenous infusion of 200 mg of ofloxacin, aqueous humor concentration was 0.33 +/- 0.19 mg/l. Our results suggest that therapeutic levels above the minimum inhibitory concentration for many bacteria cultured in endophthalmitis can be achieved in aqueous humor after either topical or oral administration, which indicates that this antibiotic passes easily through the corneal and the blood aqueous barriers.

Administration, Oral↗

PubMed2003

Somatostatin is an immunosuppressive factor in aqueous humor.

PURPOSE: To detect the presence of somatostatin (SOM) in normal aqueous humor and to characterize its immunosuppressive activity. METHODS: Fresh rabbit aqueous humor was assayed for SOM by competitive ELISA. Primed T cells stimulated through their T-cell receptor (TCR) were treated with SOM at concentrations that ranged the level of SOM found in normal aqueous humor. The T cells were assayed for proliferation, lymphokine production, and immunosuppressive activity. RESULTS: Normal rabbit aqueous humor contained 196 +/- 45 pg/mL (10(-10) M) of SOM. At concentrations between 10 and 300 pg/mL, SOM suppressed IFN-gamma production by TCR-stimulated primed T cells in culture. Frozen and thawed aqueous humor depleted of SOM no longer suppressed IFN-gamma production by the TCR-stimulated primed T cells. SOM induced TGF-beta but not IL-4 production, nor did it suppress proliferation by TCR-stimulated primed T cells. The SOM-treated T cells functioned as regulatory T cells, and this regulatory activity was neutralized by anti-alpha-MSH antibodies. Furthermore, SOM induced alpha-MSH production by the TCR-stimulated primed T cells. CONCLUSIONS: SOM is present in aqueous humor and contributes to the immunosuppressive activity of aqueous humor. Moreover, SOM induces the production of the potent immunomodulating factor alpha-MSH by TCR-stimulated primed T cells through which the SOM-treated T cells suppress other T cells. Thus, SOM can contribute to the ocular immunosuppressive microenvironment by promoting the production of immunosuppressive cytokines and inducing the activation of regulatory T cells.

Animals↗

PubMed1989

Ocular pharmacokinetics of latamoxef and cefaclor in humans. Penetration into aqueous humor.

Penetrations of latamoxef (LMOX) and cefaclor (CCL) into the aqueous humor after intravenous or oral administration were investigated in patients admitted with cataract. Concentrations of antibiotics in plasma and aqueous humor were determined periodically by microbiological assay. LMOX disappeared from plasma in a monoexponential manner with a half-life of 2.7 h after intravenous administration at a dose of 1000 mg. The maximum concentration of LMOX in aqueous humor (4.7 micrograms/ml) was observed 2 h after administration. When CCL was administered orally at a dose of 500 mg, the maximum concentration of CCL in aqueous humor was 0.53 microgram/ml 2 h after administration, whereas the maximum plasma concentration of 8.4 micrograms/ml was observed at 1 h. Pharmacokinetic analysis (simultaneous simulation) of plasma and aqueous humor concentration-time courses was done by using the best-fitting compartment model examined (modified two-compartment model). Prediction of the concentration of antibiotics in aqueous humor from the plasma concentration profile was also examined using the same compartment model in a separate experiment. The predicted concentration in aqueous humor was proved to fit reasonably with the measured concentration.

Aged↗

PubMed2000

Antithrombin III, a serpin family protease inhibitor, is a major heparin binding protein in porcine aqueous humor.

Our hypothesis is that the proteins in aqueous humor may be involved in the regulation of outflow facility through the trabecular meshwork and uveoscleral meshwork. In this study, we analyzed the profile of heparin-binding proteins present in porcine aqueous humor to identify and characterize secretory proteins with a binding affinity for heparin. A single step involving heparin-sepharose affinity chromatography of porcine aqueous humor yielded a approximately 60 kDa protein as the major heparin-binding species. This protein was specifically eluted from the column by heparin. The N-terminal sequence and immunological cross reactivity of this protein confirmed its identity as antithrombin III. Aqueous humor from different species, as well as cells from human trabecular meshwork, Schlemm's canal, and lens epithelium, contained detectable amounts of antithrombin III. Based on its known anticoagulative function in endothelial cells and effects on the production of prostacyclin, it is reasonable to speculate that antithrombin III present in aqueous humor might influence the physiology of the trabecular and uveoscleral meshwork and thereby regulate intraocular pressure.

Amino Acid Sequence↗

PubMed1986

Anaphylatoxin levels in human aqueous humor.

Radioimmunoassay was used to measure levels of C3a, C4a, and C5a in aqueous humor from 13 normal eyes, 8 noninflamed eyes with a history of surgery or inflammation, and 14 eyes with anterior uveitis. The authors were unable to measure levels of C3a, C4a, or C5a in normal aqueous humor. In noninflamed aqueous humor from eyes with a history of surgery or inflammation, the authors were unable to measure levels of C4a or C5a, but were able to measure low levels of C3a in 3/8 patients. In aqueous humor from eyes with anterior uveitis, the authors were able to measure levels of C3a in all 14 patients, C4a in 9/14 patients, and C5a in 5/14 patients. Patients with severe anterior uveitis had higher levels of C3a than those with moderate anterior uveitis. The higher ratios of anaphylatoxin to protein levels in inflamed aqueous humor, when compared to normal plasma or noninflamed aqueous humor, suggested that complement was being activated by either the classical or alternative pathways in inflamed aqueous humor. Measurable levels of C3a without detectable C4a in five patients with anterior uveitis suggested alternative pathway activation of complement.

Adolescent↗

PubMed1993

MMPs and proteinase inhibitors in the human aqueous humor.

PURPOSE: This study was performed to examine the gelatinolytic and caseinolytic activities and the levels of two proteinase inhibitors, alpha 1-proteinase inhibitor (alpha 1-antitrypsin) and alpha 2-macroglobulin, in the human aqueous humor. METHODS: Aqueous humor samples were collected during elective surgery in patients with cataracts. Zymography with gelatin- and casein-containing gels was performed. The inhibitors were examined by Western blot analyses, enzyme-linked immunosorbent assay, and dot blot assays. RESULTS: The aqueous humor contained a major band of gelatinolytic activity at a molecular weight of 66 kD and minor bands at 125, 95, and 62 kD. These gelatinases were inhibited by 10 mM ethylenediaminetetraacetic acid (EDTA) or 1,10-phenanthroline. After extended incubation (48 hours), zymography on casein-containing gels showed proteinase bands with molecular weights in the 80- to 84-kD range. Additional bands at 68 and 48 kD also were observed. All the caseinase activities were inhibited by 10 mM phenylmethylsulfonyl fluoride and 1 microgram/ml aprotinin. No inhibition was observed with 5 mM EDTA, 5 microM E-64, or 1 microM pepstatin. These results indicated that the caseinases are serine proteinases. Western blot analysis showed a 53-kD alpha 1-proteinase inhibitor band in the aqueous humor. The concentration was 32.2 +/- 9.9 micrograms/ml, constituting approximately 15% of the total protein. A 360-kD protein band immunoreactive to anti-alpha 2-macroglobulin also was detected. Its level in the aqueous humor was 3.2 +/- 1.3 micrograms/ml. CONCLUSIONS: The gelatinases, serine-like proteinases, and proteinase inhibitors found in the aqueous humor may participate in the remodeling of extracellular matrices in the trabecular meshwork and other tissues bordering the anterior chamber.

Aged↗

PubMed1997

Horseradish peroxidase: a reliable or a misleading tool for the investigations on the origin of the proteins of the aqueous humor?

The concept of the blood-aqueous barrier is largely based on the use of horseradish peroxidase (HRP). The present investigation was designed to check its reliability as a macromolecular tracer, especially with regard to the transport of plasma proteins. Rabbits were killed 5 min to 24 h after being intravenously injected with HRP. The tracer diffused rapidly, reaching the aqueous humor of the eye in 3 min or less and was detected at high concentration in the narrow space between the outer epithelial layer of the ciliary epithelium and the wall of the pervious capillaries in the stroma of the processes. HRP appeared to migrate from the blood to the posterior chamber, permeating the tight junctions, viz., the anatomical basis of the blood-aqueous barrier. It was detected at higher concentration at the anterior surface of the iris, at short time intervals; this was interpreted as penetration of the tracer from the aqueous humor of the anterior chamber. The choroid was also labeled in continuation with the reaction in the stroma of the pars plana of the ciliary body which, in turn, sometimes reached the iris root. Therefore, the pervious blood vessels of the choroid could be a source of macromolecules for the iris root. HRP also induced the formation of lysosomes in the ciliary epithelium. This can hardly be accepted as the way in which plasma proteins are physiologically transported to the aqueous humor. However, the pathway of HRP migration over short time intervals seems to be in agreement with previous research indicating that the entrance of serum albumin into the posterior chamber is the first step of its incorporation into the aqueous humor.

Acid Anhydride Hydrolases↗