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PubMed1983

Etamsylate (Dicynone) reduces aqueous humor formation and intraocular pressure in rabbits.

The rate of aqueous humor production (measured by the clearance of 125I-labeled albumin administered into the anterior chamber) and the intraocular pressure (measured via an electronic transducer) fell after subconjunctival infection of 37 mg (0.3 ml) of etamsylate (Dicynone) in rabbits. The differences between treated and untreated animals with respect to both variables were statistically significant. It is conjectured that the action of etamsylate in lowering intraocular pressure may be mediated at least in part by its reduction of aqueous humor formation.

Animals↗
PubMed1998

An experimental study of the tumour necrosis factor level in aqueous humor after transscleral fixation of intraocular lens.

PURPOSE: The tumour necrosis factor (TNF) level in aqueous humor after transscleral fixation of intraocular lens (IOL) implantation in rabbits and discuss the effect of TNF on postoperative anterior ocular inflammation. METHODS: Twenty-seven pigmented rabbits were divided into three groups. Group 1: transscleral fixation of posterior chamber (PC) IOL implantation; Group 2: Lens of rabbits was removed without IOL implantation; Group 3: the control group, without surgical intervention. On the 1st, 3rd, 7th and 14th postoperative days, aqueous humor samples were obtained. An modified double antibodies indirect sandwich ELISA was used to detected for the presence of TNF. The data were analyzed by using analysis of variance of SAS software. RESULTS: It was found that TNF level in aqueous humor was increased after transscleral fixation of IOL implantation. TNF level reached its maximum on the 14th postoperative day in the IOL implanted group. TNF level on 1st, 3rd, 7th and 14th days postoperatively was significantly the highest (p < 0.05) in IOL implanted group when compared with the other two groups. CONCLUSIONS: There is something physically related to the IOL itself which induces the secretion of TNF or this simply related to mechanical factors related to the presence of the IOL itself, and the manipulation of the iris during lens implantation stimulates TNF secretion. The increase of TNF level may play critical role in anterior ocular inflammation response after IOL implantation.

Animals↗
PubMedDate not supplied

[2 fluorophotometric methods of measuring aqueous humor flow in hypertensive patients].

Two fluorophotometric methods, by instillation and oral route, allowed the aqueous humor flow measurement and apparent outflow resistance calculation in normal and hypertensive subjects. There was no statistically significant difference between the two methods in the aqueous humor flow of hypertensive patients and normal subjects. On the contrary, there was an increase of the outflow resistance in hypertensive patients in relation to normal subjects. Finally, oral route fluorophotometry allowed the individualization and calculation of a coefficient of aqueous humor production from the iris, which is statistically increased in hypertensive in comparison with normal subjects. Subsequent studies thanks to this fluorophotometric method by oral route, which interest is certain in treated hypertensive patients, should allow to determine the action site of the drug and to quantify its efficiency.

Administration, Oral↗
PubMed1985

Effect of oxygen on aqueous humor dynamics in rabbits.

A study was made in albino rabbits of the effect on aqueous humor dynamics of 100% oxygen, administered by face mask. A mean decrease in intraocular pressure of 4.9 mm Hg was found. This was accompanied by a decrease in episcleral venous pressure of 4.5 mm Hg. Anterior chamber aqueous humor flow decreased transiently after oxygen administration but returned to pre-oxygen levels after about 60 min. It was concluded that the sustained decrease in intraocular pressure which was caused by oxygen was secondary to the decrease in episcleral venous pressure and not to a decrease in the production of aqueous humor.

Animals↗
PubMed2003

[Effects of IL-1 receptor antagonist on the level of cytokine in the rat corneal grafts and aqueous humor after corneal transplantation].

OBJECTIVE: By detecting the expression of IL-1RI and TGF-beta(1) on the normal rat cornea and graft, and the amount of IL-1 beta in the aqueous humor of normal rat eye and the eye after keratoplasty, to investigate the relationship between these cytokines and graft rejection and to observe the effects of IL-1 receptor antagonist (IL-1ra) on graft rejection. METHODS: All rats after keratoplasty were divided into five groups. Immunohistochemistry method and enzyme-linked immunosorbent assay (ELISA) were used to detect the expression of IL-1RI and TGF-beta(1) on the normal rat cornea and graft and the amount of IL- 1 beta in the aqueous humor of normal rat eye and the eye after keratoplasty at different time points: pre-rejection, acute-rejection and two weeks after surgery. RESULTS: IL-1RI could be detected in normal rat cornea. TGF-beta(1) expressed mainly in the epithelium of normal cornea, especially the basal cell layer and the basement membrane. After keratoplasty, IL-1RI and TGF-beta(1) could be detected in the corneal epithelium, stroma and endothelium, and the level of expression decreased in sequence as negative control group, 50 micro g IL-1ra group, 100 micro g IL-1ra group, 200 micro g IL-1ra group and dexamethasone group. In the acute rejection period, the expression of IL-1RI and TGF-beta(1) in the 200 micro g IL-1ra group was less than that of the 50 micro g IL-1ra group, the difference was significant (P < 0.01). The expression of IL-1RI and TGF-beta(1) in the negative control group was higher than that of all experimental groups, the difference was significant (P < 0.01). IL-1 beta was detected in normal aqueous humor; the mean level was (96.0 +/- 11.3) ng/L. In the eye after keratoplasty, the IL-1 beta level increased significantly compared to normal aqueous humor (P < 0.01). In the acute rejection period, the quantity of IL-1 beta reached its peak at (552.2 +/- 68.3) ng/L in the negative control group, which was the highest quantity of IL-1 beta in all experimental groups (P < 0.01). The IL-1 beta level in all experimental groups in the pre-rejection period had no difference compared with that in the acute rejection period (P > 0.05), but the level of IL-1 beta in the pre-rejection and rejection periods was significantly different compared with that in the post-rejection period (P < 0.01). CONCLUSIONS: IL-1RI and TGF-beta(1) play a active role in the corneal graft immunogenic rejection. IL-1 beta is a key factor in starting corneal graft rejection. The keratoplasty graft rejecting reaction can be reduced and mean survival time can be prolonged by IL-1ra, which inhibits the expression of IL-1RI and TGF-beta(1) and decreases the level of IL-1 beta in the aqueous humor.

Animals↗
PubMed2001

[Concentrations of diclofenac in aqueous humor and in plasma after i.v. injection in 59 patients undergoing cataract surgery--a prospective study].

BACKGROUND: The mean diclofenac level in the aqueous humor after i.v.-injection should be examined as an example for other systemic applied drugs. The clinical effect is to be evaluated with regard to perioperative anti-inflammatory therapy in patients undergoing cataract surgery. PATIENTS AND METHODS: In this prospective clinical study 59 patients (age 41-86 years) scheduled for phacoemulsification by the tunnel technique, received 75 mg diclofenac-sodium by short time i.v.-infusion (30 min) within an interval between 30 min and 7 h before surgery. Aqueous humor samples and one blood sample were taken at the beginning, and a second blood sample was taken at different time intervals before surgery. RESULTS: The plasma concentration of diclofenac one minute after infusion was 13,961 +/- 4277 ng/ml. The concentration decreased rapidly during the distribution phase (1305 +/- 324 ng/ml after 40 min) and reached after 336 min 419 +/- 277 ng/ml. A concentration of 83.9 ng/ml diclofenac was found for the last sampling point after 353 min in the elimination phase. The mean diclofenac concentration in the aqueous humor reached after about 60 min the highest level (21.7 +/- 12.7 ng/ml). This level decreases to 4.4 +/- 0.4 ng/ml (120 min) and 3.1 +/- 1.3 ng/ml (300 min), respectively. CONCLUSIONS: The calculated mean residence time of diclofenac molecules in aqueous humor of 123 min matched the mean disposition residence time of diclofenac in the body (119 min).

Adult↗
PubMed1999

Prolonged, contemporaneous administration of pilocarpine and timolol increases the aqueous humor pilocarpine levels in rabbits.

The purpose of this study was to gather information on the mechanism by which timolol/pilocarpine (TI/PI) combination eyedrops provide additive ocular hypotensive effects. An hypothesis, according to which the combination eyedrops prolong the intraocular permanence of PI as a consequence of decreased aqueous humor secretion induced by TI, was not supported by clear-cut literature evidence. It was thus sought to verify if repeated instillations in albino rabbits of combination TI/PI eyedrops do effectively prolong the turnover of PI. Commercial eyedrops containing 0.68% w/v TI maleate and 2.0% w/v PI hydrochloride, buffered at pH 6.8, and two reference solutions containing PI hydrochloride alone (2% w/v), buffered at pH 5.5 and 6.8, were instilled b.i.d. in albino rabbits for five days. Aqueous humor samples, analyzed after the last treatment, showed that the aqueous humor PI levels observed after administration of the combination eyedrops were significantly higher than those resulting from administration of the reference formulations. When compared with the pH 6.8 reference solution, the pH 5.5 one produced slightly higher and more sustained drug levels in the aqueous humor. The present results appear to confirm the assumption that an increased retention of PI in the aqueous humor is responsible for the additive effects on intraocular pressure reported by several authors for the combination TI/PI eyedrops.

Absorption↗
PubMed1985

Ascorbate in aqueous humor protects against myeloperoxidase-induced oxidation.

Chemotactic factors can cause polymorphonuclear leukocytes to release the contents of azurophilic granules, including the enzymes beta-glucuronidase and myeloperoxidase. In the presence of aqueous humor from the anterior chamber of the rabbit eye, the supernatant from stimulated leukocytes contains beta-glucuronidase, but myeloperoxidase is not detectable. Studies with aqueous humor and partially purified human myeloperoxidase suggest that this phenomenon is not due to a failure of enzyme release. The factor responsible for the inability to detect MPO in the assay system is heat-labile, dialyzable, and reversed by ascorbate oxidase. Comparable assay inhibition is produced by ascorbic acid at a concentration present in either human or rabbit aqueous humor. The ability of aqueous humor to protect against myeloperoxidase-induced oxidation may contribute to several diverse phenomena, including the susceptibility of the eye to Candida infection and a prolonged half-life for several inflammatory mediators in the anterior chamber.

Animals↗
PubMed1994

Melanin can deplete immunosuppressive substances from the aqueous humor.

Heavily pigmented eyes tend to experience greater inflammation than lightly pigmented eyes following trauma and surgery. The purpose of these studies was to test the possibilities that: (i) melanin augments T cell-responses by depleting or neutralizing anti-inflammatory substances that are normally present in the aqueous humor, and (ii) melanin augments extraocular T cell-mediated inflammatory responses. Two types of experiments were performed. First, the capacity of melanin-adsorbed and non-adsorbed rabbit aqueous humor to inhibit the proliferative response of the T cell line D10.G4.1 to IL-1 was tested. Non-adsorbed aqueous humor inhibited T cell proliferation to the background level in unstimulated cultures, whereas melanin-adsorbed aqueous humor enhanced the proliferation of stimulated, but not resting T cells. Next, mice were sensitized to the antigen conalbumin, and challenged in the ear pinna with conalbumin alone, conalbumin + melanin, or melanin alone and delayed-type hypersensitivity (DTH) was measured. Challenge with melanin alone caused some ear swelling, and melanin increased the DTH response to conalbumin. Our findings are consistent with the notion that melanin can augment intraocular inflammation by depleting or neutralizing the inhibitory components of normal aqueous humor, possibly exposing stimulatory components that are normally masked.

Animals↗
PubMed1994

Toxoplasma gondii-specific antibodies in the aqueous humor of cats with toxoplasmosis.

We decided to determine whether Toxoplasma gondii-specific IgM or IgG is produced locally or is deposited in the aqueous humor of T gondii-naive cats after primary or secondary inoculation with T gondii. Cats were orally inoculated with T gondii tissue cysts during weeks 0 and 36. Aqueous humor and serum T gondii-specific IgM and IgG were measured, using ELISA, during weeks 0, 2, 4, 6, 8, 12, 16, 20, 26, 34, 38, 40, 42, 44, 48, 56, 62, 66, and 72 after primary oral inoculation. Total immunoglobulin-based Goldmann-Witmer coefficients were calculated to verify intraocular antibody production. Toxoplasma gondii-specific IgM was not detected in the aqueous humor of any cat. Data indicate that cats have transient local production of T gondii-specific IgG in the aqueous humor after primary and secondary oral inoculations with T gondii tissue cysts. The intraocular immune response to systemic T gondii infection may signal ocular recruitment of antigen-specific lymphocytes that function independently from the general humoral response to T gondii infection. Cautious interpretation of results that suggest intraocular production of T gondii-specific IgG in cats with uveitis is warranted.

Animals↗
PubMed1988

Influence of indomethacin on PGE2 in rabbit aqueous humor after YAG laser photodisruption of the iris.

In an experimental study with rabbits, the influence of indomethacin on the postoperative PGE2 level in the aqueous humor was investigated, following YAG laser traumatization of the iris. Indomethacin is a drug with an inhibitory effect on the synthesis of prostaglandins. Using albino rabbits, the right eye was treated with indomethacin eye drops three times daily for 3 days. On the 4th day, high-energy YAG laser was applied to the iris of both eyes (Q-switched Nd: YAG Laser, Model Cilco Lasertek PV 135; ten photodisruptive lesions, with 50 mJ to the midperiphery of the iris). Subsequently, the rabbits were subdivided into three groups. In group 1 the aqueous humor was removed from both eyes 12 h postoperatively; in group 2 the aqueous humor was tapped 36 h after the intervention; for group 3, it was 60 h afterwards. The results from 15 rabbits were evaluated. Local indomethacin treatment was continued until tapping of the aqueous humor. As a control, another group was used with 3 rabbits without treatment. Twelve hours after YAG laser treatment there was still a clearly significant difference in the PGE2 concentrations between the eyes that had received indomethacin and the untreated eyes; 36 h postoperatively, the difference was no longer statistically significant, and after 60 h the PGE2 concentrations of the treated and untreated eyes were the same.

Animals↗
PubMed1999

Penetration of ciprofloxacin, norfloxacin and ofloxacin into the aqueous humor using different topical application modes.

BACKGROUND: A prospective study was undertaken to determine the transcorneal penetration of three topically applied fluoroquinolones into aqueous humor. METHODS: Cataract patients (n = 224) preoperatively received topically applied gyrase inhibitors (0.3% ciprofloxacin, 0.3% norfloxacin, 0.3% ofloxacin) in two different application modes. In application mode I, patients received on the day before operation 3 x 1 eye drop at 2-h intervals, and on the day of operation 3 drops at 1-h intervals. In application mode II, patients received 9 drops at 15-min intervals on the day of operation only. Just before cataract surgery 50-100 ml aqueous humor was aspirated and stored at -80 degrees C. The HPLC method was used for measuring the concentration. RESULTS: The highest concentrations of all tested antibiotics were measured after the mode of application in which one drop was given every 15 min between 06:00 and 08:00 hours before operation. In this mode, ciprofloxacin achieved a mean aqueous level of 379.8 +/- 327.8 mg/l (range 33-1388 mg/l), norfloxacin 182.1 +/- 118.1 mg/l (range 38-480 mg/l) and ofloxacin 563.9 +/- 372.1 mg/l (range 64-1455 mg/l). These mean concentration are all above the MIC90 of gram-negative bacteria like Proteus mirabilis and Escherichia coli. In some cases the concentrations of ciprofloxacin and ofloxacin, but never norfloxacin, reached therapeutic values above the MIC90 of Staphylococcus aureus and Staphylococcus epidermidis. CONCLUSIONS: The mean concentration value of 0.3% ciprofloxacin and of 0.3% ofloxacin in the aqueous humor reached the MIC90 values of the frequently occurring gram-positive and gram-negative bacteria. Of the currently available topical fluoroquinolones, ofloxacin achieved the highest aqueous humor concentration. Considering the higher antimicrobial activity of ciprofloxacin, both ciprofloxacin and ofloxacin may be useful ophthalmic agents in antibacterial management, but they are not efficient against Streptococcus pneumoniae and Pseudomonas aeruginosa.

Administration, Topical↗
PubMed1994

Aqueous humor in glaucomatous eyes contains an increased level of TGF-beta 2.

By using the highly sensitive and specific technique of enzyme-linked immunosorbent assay, we investigated the presence and amount of transforming growth factor-beta 2 (TGF-beta 2) in samples of aqueous humor obtained from 15 patients who had a clinically established diagnosis of advanced primary open-angle glaucoma (POAG), as well as from ten age-matched normal human subjects undergoing cataract surgery. The total amount of TGF-beta 2 in the samples of normal aqueous humor ranged from 0.41 to 2.24 ng ml-1 (mean +/- S.D.: 1.48 +/- 0.68 ng ml-1) of which 4.88 to 37.05% (11.99 +/- 9.95%) was intrinsically active. Compared with normal subjects, the aqueous humor from POAG patients had a statistically significantly greater amount of total TGF-beta 2 (2.70 +/- 0.76 ng ml-1, P < 0.01), as well as a higher level of intrinsically active TGF-beta 2 (0.45 +/- 0.28 ng ml-1, P < 0.05) which corresponded to 1.09 to 60.84% (18.33 +/- 15.50%) of the total amount. No linear correlation was found between the age of the subjects and the protein concentration of the aqueous humor from either normal or glaucomatous eyes, nor between the age of the patient and the total amount of TGF-beta 2. The negligible amount of TGF-beta 2 present in serum argues against its influx into the aqueous humor after breakdown of the blood-aqueous barrier that is known to occur in glaucomatous eyes; rather, our present findings support the concept of the intraocular derivation of this cytokine.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1989

[Significance of the lactate dehydrogenase level in aqueous humor in the diagnosis of retinoblastoma].

Aqueous humor LDH levels of 104 patients (113 eyes) were determined. In 18 patients (18 eyes) with retinoblastoma, the range was 3,850.8-86,717.3 mumol.s-1/L, very significantly higher than those of cataract, glaucoma, retinal detachment, and penetrating eye injury (P less than 0.01). The LDH values of 7 eyes of chronic endophthalmitis were 1,917.1-84,250.2 mumol.s-1/L and that of 1 eye with choroidal malignant melanoma was 19,553.9 mumol.s-1/L, the differences being insignificant (P greater than 0.05). The authors deemed that aqueous LDH levels exceeding 16,670 mumol.s-1/L could be indicative of retinoblastoma; however, with a pseudo-positive rate of 28.6% and a pseudo-negative rate of 16.7%, its practical use in differential diagnosis was limited.

Aqueous Humor↗
PubMed1990

A new approach to the study of aqueous humor dynamics by measuring the intensity of Tyndall's effect.

A technique is described for studying aqueous humor dynamics by measuring aqueous flare intensity with the laser flare-cell meter. Aqueous flare intensity measured with this instrument was converted into the equivalent human albumin concentration (Ca). A differential equation was given to express the relationship among Ca, aqueous flow rate, plasma protein concentration, anterior chamber volume and the coefficient of entry into the anterior chamber (k(in)) for plasma protein. When k(in) is constant, the time course of changes in aqueous flow rate can be determined from a series of measurements of Ca with the laser flare-cell meter. Using this technique, we assessed the effects of oral acetazolamide on aqueous flow rate. Oral administration of 500 mg acetazolamide decreased aqueous flow rate from 1.25 to 8 hours post-administration, with a maximum reduction of 40% at 1.75 hours post-administration. The validity of this technique was confirmed by comparing the results with those of fluorophotometric measurements. In situations where k(in) is affected by ocular procedures, the time course of changes in k(in) can be monitored by measuring Ca, aqueous flow rate and anterior chamber volume in the same eye. We applied this method to investigate the effects of pilocarpine on the rate of protein entry into the aqueous humor. Single instillation of 1% pilocarpine increased k(in) from 4 to more than 10 hours after the application, with a maximum increase of 37% observed at 9 hours post-application.

Acetazolamide↗
PubMed2005

Blebbistatin, a novel inhibitor of myosin II ATPase activity, increases aqueous humor outflow facility in perfused enucleated porcine eyes.

PURPOSE: To investigate the specific role of myosin II, a critical biochemical determinant of cellular contraction, in modulation of aqueous humor outflow facility through the trabecular meshwork (TM) pathway. METHODS: Expression of the nonmuscle myosin II heavy chains (IIA, IIB, and IIC) in human TM and ciliary body (CB) cells was determined by RT-PCR analyses. The effects of inhibition of myosin II on cell morphology, actomyosin organization, and cell adhesions were evaluated in porcine TM and CB cells treated with blebbistatin, a cell-permeable, specific inhibitor of myosin II adenosine triphosphatase (ATPase) activity. Changes in aqueous humor outflow facility were determined in enucleated porcine eyes by using a constant-pressure Grant perfusion model system. Ultrastructural integrity of the outflow pathway in drug-perfused eyes was analyzed by transmission electron microscopy. RESULTS: Expression of nonmuscle myosin IIA and IIB was confirmed in both human TM and CB cells. Confluent cultures of primary porcine TM and CB cells treated with blebbistatin in the presence of serum revealed dose (10-200 microM)-dependent changes in cell morphology, decreases in actin stress fiber content and in focal adhesions and adherens junctions. These changes were found to be reversible within 24 hours of drug withdrawal from the cell culture media. Blebbistatin did not affect the status of myosin light chain phosphorylation in TM cells. Perfusion of enucleated porcine eyes for 5 hours with 100 and 200 microM blebbistatin produced a significant increase (P < 0.01, n = 7) in aqueous outflow facility (53% and 64%, respectively) from the baseline facility, compared with a 21% facility increase in sham control specimens. The integrity of the inner wall of aqueous plexi in drug-perfused porcine eyes was found to be intact, and TM cell morphology appeared to be similar to that noted in sham-treated eyes. CONCLUSIONS: These data demonstrate that selective inhibition of myosin II in the aqueous humor outflow pathway leads to increased aqueous outflow facility, suggesting a critical role for myosin II in the regulation of aqueous humor outflow facility. This study also suggests myosin II as a potential therapeutic target for lowering intraocular pressure in patients with glaucoma.

Adenosine Triphosphatases↗
PubMed1996

Rapid liquid chromatographic assay of ciprofloxacin in human aqueous humor.

A simple, selective and sensitive method has been developed to determine ciprofloxacin in human aqueous humor. Separation of ciprofloxacin was carried out with pipemidic acid as internal standard using a Novapak C18 reversed-phase cartridge column (100 x 8 mm i.d., particle size 4 microns) and a mobile phase consisting of methanol-acetonitrile-citric acid (0.4 M) (3:1:10, v/v/v) at a flow rate of 1 ml min-1. The column effluent was monitored with fluorescence detection at 278 nm (excitation) and 450 nm (emission) after direct injection. The retention times were 4.88 min for pipemidic acid and 7.52 min for ciprofloxacin. The within-day and day-to-day reproducibilities were less than 7% for ciprofloxacin at 0.1 and 1 microgram ml-1 (n = 6). The mean recovery from aqueous humor was found to be 101.37 +/- 6.7% for ciprofloxacin at 0.1 micrograms ml-1 (n = 6 and the detection limit corresponding to a signal-to-noise ratio of 2.5:1 was 250 pg ml-1. The method was shown to be suitable for determining ciprofloxacin levels in human aqueous humor samples.

Aged↗