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Lack of circadian change of concentration of C-type natriuretic peptide in rabbit aqueous humor.

PURPOSE: To determine whether there is a circadian change of the concentration of C-type natriuretic peptide (CNP) in rabbit aqueous humor. METHODS: Forty-one male white New Zealand rabbits were submitted to a 12 h light and 12 dark lighting schedule; lights on was at 0 h, lights off at 12 h. C-type natriuretic peptide was assayed at 3 light (2 h, 6 h and 10 h) and 3 dark (14,18 and 22 h) times. All groups consisted of four animals but two had more animals to increase the power of tests (6 h, n = 12; 22 h, n = 13). Dependence between the two eyes was tested by Pearson's correlation. The mean of two eyes was considered for analysis. Differences in concentration in pg/200 ml were evaluated by one-way ANOVA, t test and COSINOR analysis. RESULTS: There were no significant differences between the 6 analyzed groups (one-way ANOVA p = 0.157). Pooled into two groups (light and dark), the C-type natriuretic peptide concentration of the light group was lower, 2.626 +/- 0.92 pg/200 ml compared with the dark group 3.02 +/- 1.16 pg/200 ml but did not reach a significant difference (t test; p = 0.23). COSINOR analysis was not statistically significant (R% = 7.72 p = 0.209). CONCLUSION: These data demonstrate that the concentration of CNP in aqueous humor did not show a statistically significant circadian change in rabbits entrained to a 12 h light: 12 h dark lighting schedule.

Analysis of Variance↗

A simple method of measuring aqueous humor flow with intravitreal fluoresceinated dextrans.

Fluoresceinated dextran was injected into the vitreous cavity of rabbits and its concentration was followed in the vitreous and aqueous humors for a period of weeks by slip-lamp fluorometry. The concentrations in both fluids fell in parallel and in an exponential manner where the time constant was determined by the molecular weight of the dextran. The rate of movement of the dextran from the vitreous into the anterior chamber is controlled by passive diffusion and may be assumed to be relatively steady; accordingly, the faster the rate of flow in the aqueous humor the lower will be the concentration of dextran in it. Circadian variations in the aqueous flow were observed, a drop at night time being noted. These were small enough for changes due to systemic influences to be determined; in particular, it was found that general anesthesia with ketamine had no significant effect. The ratio of the concentration in the anterior chambers of the two eyes of one animal normally remains constant with time. Changes in the ratio can be used to determine the influence of unilateral interventions. This was illustrated by the use of adrenergic drops which led to a brief rise in flow rate and then a longer-lasting fall, and by X-ray irradiation with 1000 rads, which caused an immediate fall in flow rate interrupted for a time by a phase of increased flow. An absolute estimate of the aqueous flow can be derived from measurements of the total amount of dextran in the eye and its concentration in the anterior chamber. A definite value has not yet been established owing to ambiguities in determining the former quantity.

Anesthesia, General↗

Comparison of dorzolamide and timolol as suppressors of aqueous humor flow in humans.

OBJECTIVES: To measure the effectiveness of topical 2% dorzolamide hydrochloride (Trusopt, Merck & Co Inc, Whitehouse Station, NJ) as a suppressor of aqueous humor flow in the human eye as compared with the effectiveness of 0.5% timolol maleate (Timoptic, Merck & Co Inc) and to measure the additivity of the 2 drugs. DESIGN: A randomized, double-masked, placebo-controlled study of 40 human subjects was carried out in 2 academic centers (Mayo Clinic, Rochester, Minn, and University of Uppsala, Uppsala, Sweden). The rate of aqueous flow was measured from 8 AM to 4 PM by means of fluorophotometry after administration of doses of each drug singly and both drugs together. RESULTS: Dorzolamide reduced aqueous flow from 3.07 +/- 0.63 microL/min (mean +/- SD) to 2.53 +/- 0.60 microL/min, a reduction of 18% (P < .001). Timolol reduced aqueous flow from the same beginning rate to 1.64 +/- 0.35 microL/min, a reduction of 47% (P < .001). The inhibitory effect of timolol was 2.6 times the inhibitory effect of dorzolamide (P < .001). The 2 drugs were almost completely additive, and together reduced the flow to 1.37 +/- 0.33 microL/min, a reduction of 55%. Consistent effects were observed on intraocular pressure. CONCLUSIONS: Timolol is more effective than dorzolamide as a suppressor of aqueous humor flow in the normal human eye. Timolol and dorzolamide are additive in their effects, both on aqueous flow and intraocular pressure.

Adrenergic beta-Antagonists↗

Comparison of fluconazole pharmacokinetics in serum, aqueous humor, vitreous humor, and cerebrospinal fluid following a single dose and at steady state.

The objective of this study was to characterize the pharmacokinetic parameters and penetration of fluconazole following a single dose in the serum, aqueous humor, vitreous humor and cerebrospinal fluid (CSF) of non pigmented rabbits using serial sampling techniques and to determine if the pharmacokinetic parameters in the eye and CSF are similar. Twenty healthy male rabbits received intravenous fluconazole 20 mg/kg as a single dose or 20 mg/kg every 12 hours for 4 doses. Serum, aqueous humor, vitreous humor and CSF samples were taken 15 minutes after the initial intravenous injection and hourly thereafter for six hours. Fluconazole concentrations were determined by microbiological assay. Pharmacokinetic analyses were performed using a nonlinear least-square regression program. Fluconazole's penetration in all anatomical compartments was > 70% than in the serum. Similar elimination half-lives and time to reach maximum concentrations were noted in all compartments. While mean concentrations in each anatomical compartment were similar in animals receiving a single dose or among those at serum steady state, the mean concentrations achieved in the serum, aqueous and vitreous humors and CSF were between 1.82 and 2.17 times higher at serum steady state than following a single dose. At serum concentrations that are comparable to those in humans, the penetration of fluconazole into the noninflamed aqueous and vitreous humors and CSF were > or = 70%. The CSF and ocular pharmacokinetic parameters closely resembled each other, so that either could be used as a surrogate for the other.

Animals↗

[The effect of bunazosin hydrochloride on intraocular pressure and aqueous humor dynamics in human].

The effects of bunazosin hydrochloride, a new highly selective alpha 1 adrenergic antagonist, on the intraocular pressure (IOP) and aqueous humor dynamics in healthy human volunteers were studied. Unilateral topical administration of 0.1% bunazosin significantly lowered IOP from 1 to 10 hrs in bunazosin-treated eyes, and from 2 to 8 hrs in contralateral placebo-treated eyes, with its maximum reduction at approximately 3 hrs, when the IOP decreased 5.0 mmHg in treated eyes, and 3.5 mmHg in contralateral eyes from the baseline, respectively. Fluorophotometrically measured aqueous humor flow rates did not change significantly either in treated or contralateral eyes. Bunazosin caused significant reduction of systolic and diastolic blood pressure 5 hr after application. The difference in pupil diameter between treated and contralateral eyes was found to be statistically significant from 1 to 5 hrs. A small but significant increase in anterior chamber depth also was observed from 2 to 6 hrs. Pulse rate and refraction were not substantially altered. There was moderate conjunctival vessel dilation, however, no serious complications were encountered. The results suggest that bunazosin hydrochloride appears to have great clinical potential for ocular hypotensive therapy.

Adrenergic alpha-Antagonists↗

Short-term clinical study on a new aqueous humor drainage implant for refractory glaucoma.

OBJECTIVE: To investigate the therapeutic effect of a new aqueous humor drainage (HAD) implant made in China for the treatment of refractory glaucoma. METHODS: The implant was designed by ourselves and manufactured by Beijing Rubber Products Design and Research Institute. From July, 1993 to September, 1995, we observed 40 patients (41 eyes) with refractory glaucoma treated by implantation surgery, including 16 eyes with neovascular glaucoma (NVG) and 25 eyes with non-neovascular glaucoma (NNVG). RESULTS: The mean period of postoperative follow-up was 9.2 (range, from 3-27) months, the intraocular pressure (IOP) was lowered from preoperative 7.20 +/- 1.51 kPa to postoperative 2.40 +/- 1.33 kPa in NVG group and from preoperative 6.27 +/- 1.07 kPa to postoperative 2.00 +/- 2.93 kPa in NNVG group. The success rate was 81% in NVG group and 84% in NNVG group. The common postoperative complications were flat anterior chamber, hyphema and choroidal detachment. CONCLUSIONS: Our newly designed aqueous humor drainage implant is an economical implant in China and one of the alternative and effective methods for the treatment of refractory glaucoma. It can be widely used in clinics.

Adult↗

A new method for the evacuation of aqueous humor in uncontrolled glaucoma. The vitreo-tenonian tube.

The vitreo-tenonian tube is a new procedure, used in uncontrolled glaucoma, for the drainage of aqueous humor. It presents three original characteristics: it is made of a stainless metal, it is implanted in the posterior segment after vitrectomy and it drains the aqueous humor in the subtenonian space. We will describe first the surgical technique for the implantation of the tube, and then we will present the results of the first eight cases treated by this method. The advantages and drawbacks of this type of drainage are discussed: they are compared with the other surgical techniques used in cases of glaucoma which is uncontrolled by the classical methods.

Aqueous Humor↗

Comparison of T helper/T suppressor ratios in aqueous humor and blood samples by flow cytometric analysis.

This study investigates the T lymphocyte role in the production of the specific immunosuppressive environment that occupies the anterior segment of the eye. Aqueous and peripheral venous blood samples were taken from 23 patients who were operated because of senile cataract. In all samples, T helper/T suppressor ratios were established and differences between aqueous and blood samples were investigated by t statistic and Mann-Whitney U test. We found significantly more T suppressor cell activity in aqueous humor than in peripheral blood (p < 0.05). We think that high T suppressor concentration in aqueous humor plays an important role in the induction of the immunosuppressive microenvironment that occupies the anterior chamber of the eye.

Aged↗

Patterns of intraocular pressure elevation after aqueous humor outflow obstruction in rats.

PURPOSE: To determine the diural intraocular pressure (IOP) response of Brown Norway rat eyes after sclerosis of the aqueous humor outflow pathways and its relationship to optic nerve damage. METHODS: Hypertonic saline was injected into a single episcleral vein in 17 animals and awake IOP measured in both the light and dark phases of the circadian cycle for 34 days. Mean IOP for light and dark phases during the experimental period were compared with the respective pressures of the uninjected fellow eyes. Optic nerve cross sections from each nerve were graded for injury by five independent masked observers. RESULTS: For fellow eyes, mean light- and dark-phase IOP was 21 +/- 1 and 31 +/- 1 mm Hg, respectively. For four experimental eyes, mean IOPs for both phases were not altered. Six eyes demonstrated significant mean IOP elevations only during the dark phase. Of these, five showed persistent, large circadian oscillations, and four had partial optic nerve lesions. The remaining seven eyes experienced significant IOP elevations during both phases, and all had extensive optic nerve damage. CONCLUSIONS: Episcleral vein injection of hypertonic saline is more likely to increase IOP during the dark phase than the light. This is consistent with aqueous outflow obstruction superimposed on a circadian rhythm of aqueous humor production. Because these periodic IOP elevations produced optic nerve lesions, both light- and dark-phase IOP determinations are necessary for accurate correlation of IOP history to optic nerve damage in animals housed in a light- dark environment.

Animals↗

[Ocular toxoplasmosis antibodies in aqueous humor and serum].

BACKGROUND: The diagnosis of ocular toxoplasmosis is mainly based on ophthalmological examination but might be difficult to establish in some cases. The purpose of our study was to evaluate the value of aqueous humor and serum analysis in ocular toxoplasmosis. PATIENTS AND METHODS: We analyzed the avidity of toxoplasma-specific IgG in aqueous humor and serum samples from 50 patients with toxoplasmic retinochoroiditis, with 25 patients with uveitis posterior or panuveitis serving as controls. RESULTS: Specific intraocular antibody synthesis could be confirmed in 49 patients (98%). In two patients (8%) of the control group, antibody synthesis was detected (false positive). Forty-nine patients with diagnoses of ocular toxoplasmosis were positive for serum anti-T. gondii IgG, but only three patients had increased IgM levels. CONCLUSIONS: Analysis of local antibody production is a reliable method for confirming or excluding a suspected clinical diagnosis of toxoplasma retinochoroiditis. The determination of toxoplasma antibodies in the patients' serum is of limited value.

Adolescent↗

[Qualitative and quantitative determination of prealbumin, retinol-binding protein, Gc-globulin and C4-component in aqueous humor (author's transl)].

By using the combined disc-immunomethod, prealbumin, retinol-binding protein Gc-globulin, and C4-component were identified in human aqueous humor. These proteins can be quantitatively analyzed by single radial immuno-diffusion. The quantiative determination of retinol-binding protein and C4-component in aqueous humor could be of diagnostic value because retinol-binding protein is capable of transporting retinol (vitamin A), and C4-component is implicated in immunologic reactions. Moreover, it is noteworthy that by these immunologic methods it is possible to determine protein concentrations below 0.05 mg/100 ml.

Aqueous Humor↗

Elevated lactic acid dehydrogenase in aqueous humor in an eye without retinoblastoma.

A 14-month-old boy had a microphthalmic left eye. An anterior chamber paracentesis was performed six days after examination under anesthesia. Lactic acid dehydrogenase (LDH) level in the aqueous humor was 1,158 mu and was 202 mu in the serum. The aqueous humor/serum LDH ratio was 5.73. This eye was eventually enucleated and found to have retinal dysplasia and diffuse hemorrhagic necrosis. There was no eividence of retinoblastoma. The elevated LDH level in aqueous humor was probably secondary to the ocular tissue necrosis and hemorrhage. This false-positive result emphasizes the limitation of using the aqueous humor/serum LDH ratio to distinguish eyes with retinoblastoma from those without retinoblastoma.

Aqueous Humor↗

The presence and properties of myocilin in the aqueous humor.

PURPOSE: To determine whether myocilin is present in the aqueous humor (AH) and to examine certain properties of this protein. METHODS: Human AH was obtained at the time of either glaucoma surgery or cataract extraction. Monkey AH was obtained at the time of death, and bovine aqueous was obtained from eyes delivered from an abattoir. Column chromatography was performed on aqueous samples to determine the approximate size of the myocilin present. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and western blot analysis were performed using antibody prepared against a peptide sequence in myocilin. Analysis of the bovine proteins present in AH that were retained by a microporous filter was also performed using western blot analysis. RESULTS: By western blot analysis, myocilin was present in human, monkey, and bovine AH. The apparent molecular size of the myocilin present in the AH were greater than 250,000 Da, when quantified with a gel filtration column. Myocilin appeared to be hydrophobic and was one of the proteins that was retained on microporous filters that were obstructed by AH. CONCLUSIONS: Myocilin is a constituent in the AH. It appears that myocilin is a hydrophobic protein that may exist in an oligomeric state or in association with other proteins. Myocilin is retained by microporous filters and may be involved in the obstruction of these filters that occurs when AH is perfused through them.

Animals↗

Sulfonamides and secretion of aqueous humor.

The connection between carbonic anhydrase and the formation of aqueous humor arose in the decade 1950-1960 when a number of experiments of differing types showed that HCO3- ion catalytically formed in the ciliary process from CO2 was a principal element in the production of the aqueous. It was soon shown that inhibitors of the enzyme, given systemically, slowed HCO3- formation and sodium and fluid transport and thereby lowered intraocular flow and pressure in normal vertebrates and in patients with glaucoma. In the past 15 years successful efforts have been made to produce sulfonamide inhibitors that reach the ciliary process after local application to the cornea. The effects of locally acting sulfonamides are largely due to their amphoteric properties. They are soluble in both lipid and non-lipid media and penetrate cornea and sclera to reach ciliary process. Potency against carbonic anhydrase II is of the order of K(I) = 10(-9) M, so that topical application inhibits essentially all enzyme in the processes and is an effective nontoxic treatment for glaucoma.

Aqueous Humor↗

The effect of oral metyrapone on aqueous humor dynamics in normal human eyes.

We studied the possible influence of oral metyrapone tartrate (which inhibits the adrenal biosynthesis of cortisol) on the rate of aqueous humor flow in 9 eyes of 8 normal subjects by fluorophotometry. On the control day, the mean value of Ko was 1.04 +/- 0.32 min-1 x 10(-2), where Ko was the loss coefficient from the anterior chamber. On the metyrapone trial day, the mean value of Ko was 0.63 +/- 0.15 min-1 x 10(-2). The mean difference in Ko between the two periods was significant (P less than 0.005). These results indicated that systemic metyrapone administration decreases the rate of aqueous humor flow.

Administration, Oral↗

Studies of aqueous humor proteins in rabbits after posterior chamber lens implantation.

In 13 rabbits, 1 month to 1 year after posterior chamber lens implantation/polymethylmetacrylate/, the level of aqueous humor proteins was evaluated and the proteins separation in polyacylamide gel was performed. The studies were also carried out in unoperated eyes of the same animals and control group was composed of the eyes before surgery. It was found that in pseudophakic eyes an increased level of proteins remained during the whole year/the highest one month after surgery, slowly decreasing afterwards/, with the appearance of additional fractions. The moderate increase of the proteins concentration was also observed in unoperated eyes. The increase of aqueous humor proteins in pseudophakic eyes indicates that the presence of polymethyl metacrylate is not completely indifferent to the eyeball in spite of the suggestions derived from the clinical observations.

Animals↗

[Aqueous humor levels of gentamicin after parenteral, subconjunctival and topical administration (aithor's transl)].

The purpose of this study was to determine the concentration of Gentamicin in blood serum and primary aqueous humor at varying periods of time after intravenous, intramuscular, subconjunctival and topical administration of Gentamicin. Therapeutic effective levels in primary aqueous humor were measured only after subconjunctival injections. The only broad spectrum antibiotics are the aminoglykosides Gentamicin, Tobramycin, Sisomicin and Amikacin. For prompt treatment of bacterial endophthalmitis without bacterial culture and antibiotic sensitivity testing therefore subconjunctival injection of Gentamicin is necessary.

Administration, Topical↗

Probability of the presence of glycosaminoglycans in aqueous humor.

The crossed immunoelectrophoretic pattern of 62 eyes was reexamined, and 6 cases were selected for their abnormal patterns that demonstrated the presence of glycosaminoglycans in aqueous humor. Three of these cases were exfoliation syndrome, one was pigment liberation syndrome, and the other two were rhegmatogeneous retinal detachment. The abnormal electrophoretic patterns showed peculiar tailing and a biphasic pattern in albumin. Similar patterns could be reproduced in vitro by adding chondroitin sulfate to normal aqueous humor. Abnormal overproduction of glycosaminoglycans in exfoliation syndrome was indicated. Similar tailing of albumin was also noticed in 2 of 3 cases of rhegmatogeneous retinal detachment. It is supposed that the glycosaminoglycans produced by visual cells pass through the retinal break and vitreous cavity on the way to the anterior chamber. The Schwartz syndrome may be explained by this mechanism.

Adult↗