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PubMed1997

[Levels of selected cytokines in aqueous humor of patients with cataract extraction].

AIM: The purpose of the investigation was to evaluate the presence of IL-1 beta, IL-2, IL-6, IL-8, TNF-alpha, IFN-gamma in aqueous humor of patients with cataract. MATERIALS AND METHOD: Aqueous humor was taken from 29 patients during extracapsular cataract extraction. The presence of cytokines was evaluated using immunoenzymatic methods. RESULTS: IL-2, IL-6, IL-8, TNF-alpha and IFN-gamma were found in all aqueous humor samples. There was no evidence for the presence of IL-1 beta. CONCLUSION: Cytokines may play role in the inflammation process after extracapsular cataract extraction.

Aged↗
PubMed1996

Matrix metalloproteinases and their inhibitors in aqueous humor.

Matrix metalloproteinase activity is the rate-limiting step in extracellular matrix degradation. One mechanism by which metalloproteinases are regulated is through the activity of their endogenous inhibitors, the tissue inhibitors of metalloproteinases. Since metalloproteinase activity is a key component of the angiogenic process and many anterior segment structures are largely avascular, we became interested in examining aqueous humor for the presence of metalloproteinases and their endogenous inhibitors. Using zymography, we have identified the presence of several metalloproteinases in normal aqueous humor. Treatment with 4-aminophenylmercuric acetate, an organomercurial which activates latent metalloproteinases, revealed that all metalloproteinases were in their active state. By Western blot analysis, normal aqueous humor was also found to contain at least two tissue inhibitors of metalloproteinases. Subsequent partial purification by two successive chromatographic steps revealed the presence of inhibitory activity against collagenase, endothelial cell DNA synthesis, and angiogenesis on the chick chorioallantoic membrane. The presence of metalloproteinases and their inhibitors in normal aqueous humor, a fluid which bathes avascular ocular structures, suggests that future studies should examine whether an imbalance in this protease/inhibitor family may contribute to the anterior chamber extracellular matrix alterations associated with diseases such as ocular neovascularization and glaucoma.

Animals↗
PubMed1979

[The determination of IgE in human aqueous humor in a case of intraocular parasitosis (ophthalmomviasis interna) (author's transl)].

A case of intraocular myasis is here reported, as well as the difficulties of diagnosis--mostly too late--of this disease, which is rare in Europe and the northern hemisphere and which leads, almost invariably, to functional or even anatomical loss of the eye.--The determination of IgE in human aqueous humor (ah) and corresponding serum (s) by means of the ultrasensitive and quite simple PRIST method could represent a possibility of timely diagnosis, and this theoretically too in the case of other, much more frequent oculoparasitosis cases.--A retrospective study of the preoperative aqueous humor of the ophthalmomyiasis case presented here revealed an IgE concentration of 113 U/ml in the aqueous humor, with only 3 U/ml (1 U congruent to 2 ng) in the corresponding serum. A simple serum-IgES-determination would not have permitted the diagnosis--at least not in the case examined--just as little as numeration of eosinophilic granulocytes in blood and/or aqueous humor.

Aqueous Humor↗
PubMed2005

Effects of cholesterol-lowering statins on the aqueous humor outflow pathway.

PURPOSE: To investigate the effects of cholesterol-lowering statin drugs on trabecular meshwork cellular properties and aqueous humor outflow. METHODS: Primary cell cultures of porcine trabecular meshwork (PTM) and ciliary body (PCB) were treated with either lovastatin or compactin, to determine the effects of statins on cell shape, actin cytoskeletal organization, and cell-extracellular matrix interactions (focal adhesions) by immunofluorescence staining. Changes in myosin light-chain (MLC) phosphorylation were evaluated by Western blot analysis. Changes in Rho GTPase content of membrane fractions from lovastatin-treated PTM cells were assessed by Western blot analysis. A constant-flow, organ-culture perfusion system was used to measure the effects of statins on aqueous humor outflow facility in the anterior segments of porcine eyes. RESULTS: PTM and PCB cells treated with lovastatin or compactin exhibited dramatic changes in cell shape and cytoskeletal organization within 24 hours, consisting of cell rounding, actin depolymerization, and decreased focal adhesions. These effects were found to be reversible on supplementation with geranylgeranyl pyrophosphate. Both lovastatin and compactin decreased MLC phosphorylation in PTM and PCB cells. PTM cells treated with lovastatin exhibited marked decreases in membrane-bound Rho GTPase. In addition, perfusion of organ-cultured porcine eye anterior segments with 100 microM lovastatin for 96 hours caused a significant increase in aqueous humor outflow facility (110%) compared with control eyes, in a reversible manner. CONCLUSIONS: This study demonstrates that the statin drugs lovastatin and compactin induce changes in cell shape and actin cytoskeletal organization and decrease MLC phosphorylation in PTM and PCB cells, all of which are events that are likely to lead to cellular and tissue relaxation. In addition, these effects of the statins appear to be mediated by inhibition of isoprenylation of the small GTP-binding proteins such as Rho GTPase. An important finding is that statins exert an ocular hypotensive response in an organ-culture perfusion model, indicating the potential for this class of drugs in glaucoma therapy.

Actins↗
PubMed2007

The positive role of lumbar puncture in the diagnosis of Vogt-Koyanagi-Harada disease: lymphocyte subsets in the aqueous humor and cerebrospinal fluid.

PURPOSE AND METHODS: Activated T cells are believed to be important at the inflammatory sites in the pathogenesis of Vogt-Koyanagi-Harada disease. Patients are often affected by meningitis and uveitis. In this work, to examine the positive role of lumbar puncture in the diagnosis of VKH disease, we analyzed and compared the surface markers of aqueous humor cells, cerebrospinal fluid cells, and peripheral blood lymphocytes by use of flow cytometry. RESULTS: Most lymphocytes were T cells. In aqueous humor and cerebrospinal fluid, numbers of CD3(+), CD4(+), and CD4(+)CD45RO(+) cells were significantly greater than in peripheral blood lymphocytes (P < 0.01). The CD4(+)/CD8(+) ratio for aqueous humor and cerebrospinal fluid was significantly higher than that for peripheral blood cells (P < 0.01). Four weeks after starting systemic corticosteroid treatment, numbers of CD4(+) and CD4(+)CD45RO(+) cells in cerebrospinal fluid were significantly lower than before treatment. CONCLUSIONS: Profiles of surface markers were similar for cerebrospinal fluid and aqueous humor, but apparently different from that for peripheral blood cells. This suggests that cerebrospinal fluid may reflect the active local immunological reaction at sites affected by the disease, i.e. the uvea and the meninges.

Acute Disease↗
PubMed1989

Ferroxidase activity increases in the aqueous humor during the ocular inflammatory response.

Ferroxidase activity was increased in the aqueous humor from inflamed eyes compared to their uninflamed contralateral controls 24 h after intravitreal injection of 10 ng of endotoxin. Changes in ferroxidase activity and copper concentration paralleled each other indicating that the plasma copper transport protein ceruloplasmin (plasma ferroxidase) entered the inflamed aqueous humor from plasma through disrupted blood ocular barriers. The presence of ferroxidase activity would facilitate the removal of potentially damaging, free radical generating Fe+2. Therefore, plasma proteins may perform important protective functions in the inflamed intraocular fluids.

Animals↗
PubMed2006

Connexin43 is required for production of the aqueous humor in the murine eye.

Connexin43 is a major component of the gap junctions between pigmented and non-pigmented cells of the double-layered epithelium in the ciliary body of the eye. We directly tested the hypothesis that gap junctions play a crucial role in the production of the aqueous humor by inactivating the GJA1 (connexin43) gene in the pigmented epithelium with cre-loxP technology. To accomplish this, we crossed a line expressing cre recombinase driven by the nestin promoter and a line with floxed connexin43 alleles. Resultant lines exhibited loss of connexin43 from the pigmented epithelium, iris, retinal pigment epithelium and the lens. We observed plasma proteins in the aqueous humor and pathological changes consistent with a loss of intraocular pressure. As the ciliary body is responsible for aqueous humor production, these data support the hypothesis that the gap junctions between pigmented and non-pigmented epithelium are necessary for production of the aqueous humor that is in turn required for the generation of normal intraocular pressure and nourishment of the postnatal lens. The loss of connexin43 expression in the iris correlated with a separation of the posterior pigmented epithelium from the anterior myoepithelium and with meiosis, possibly resulting from a loss of function of the dilator pupillae.

Animals↗
PubMed1986

Effect of timolol on aqueous humor protein concentration in the human eye.

We performed a double-masked, controlled study investigating the increase in the protein concentration in aqueous humor after topical timolol maleate administration. Forty patients scheduled to undergo intracapsular cataract surgery were included in the study. Either timolol ophthalmic solution or the vehicle of timolol alone (control) were applied topically in a randomized fashion, and aqueous humor was collected during surgery. Protein concentrations were determined by gel-filtration chromatography. The total protein concentration as well as the concentration of high and medium molecular weight proteins were significantly elevated in the timolol-treated group. The relation of the levels of the three different molecular weight classes did not differ significantly between the two groups, indicating that undisturbed protein filtration in the face of reduced aqueous humor production--and not a change in the permeability of the blood-aqueous barrier--is responsible for the increase in concentration.

Aqueous Humor↗
PubMed2003

Effect of WIN 55212-2, a cannabinoid receptor agonist, on aqueous humor dynamics in monkeys.

OBJECTIVE: To evaluate the effects of WIN 55212-2, a cannabinoid receptor agonist, on intraocular pressure and aqueous humor dynamics in normal monkeys and monkeys with glaucoma. METHODS: Intraocular pressure was measured prior to and up to 6 hours after the topical administration of WIN 55212-2 to 1 eye of 5 normal monkeys and to the glaucomatous eye of 8 monkeys with unilateral laser-induced glaucoma. Tonographic outflow facility and fluorophotometric flow rates of aqueous humor were measured in 6 normal monkeys before and after treatment. RESULTS: In normal monkeys, a single dose of WIN 55212-2 reduced intraocular pressure for 4, 5, or 6 hours, with a maximum reduction of 1.4 +/- 0.4 (mean +/- SEM) mm Hg, 2.9 +/- 0.4 mm Hg, and 3.4 +/- 0.6 mm Hg following the 0.07%, 0.2%, and 0.5% concentrations, respectively (P =.08). In 8 glaucomatous monkey eyes, the ocular hypotensive effect was maintained for 5 days with twice-daily administration of 0.5% WIN 55212-2. Outflow facility was unchanged (P =.34) and aqueous humor flow was decreased by 18% (P =.04) in the treated eyes compared with vehicle-treated contralateral control eyes in normal monkeys. CONCLUSIONS: WIN 55212-2, a cannabinoid agonist at the CB(1) receptor, reduces intraocular pressure in both normal and glaucomatous monkey eyes. A decrease of aqueous flow appears to account for the intraocular pressure reduction in normal monkey eyes. CLINICAL RELEVANCE: Cannabinoid agonists at the CB(1) receptor, a new class of antiglaucoma agents that is different from currently used clinical drugs, may have clinical potential.

Administration, Topical↗
PubMed1995

[Quantitative assessment of blood-aqueous humor barrier permeability using densitometry methods combined with high performance thin layer chromatography].

The paper presents an original method of examining blood-aqueous humor permeability. The examinations were performed on grey rabbits that had been intravenously injected 10% fluorescein solution. Subsequently, at definite time intervals from the moment of the administration, fluid of the anterior chamber was taken in which the amount of aqueous fluorescein permeating to aqueous humor was measured. The measurements were performed using the method of high potency thin layer chromatography (HPTLC) in DS type chambers. Examination results were presented as densitometry, and the area of individual points was counted using a computer programme. This method yielded a diagram quantitatively presenting fluorescein permeation from the blood to the aqueous humor.

Animals↗
PubMed1995

[Fluconazole level in aqueous humor after oral drug administration in humans].

For 2 years fluconazole, a triazole antimycotic, has been available for treatment of systemic mycosis. Compared to amphotericin B fewer severe side effects have been reported. So far, no data have been published as to its penetration into the human eye. In the present study, 20 cataract patients were given 200 mg fluconazole (0.5 to 8 h preoperatively. During the cataract operation 0.1 ml of the aqueous was removed as well as 10 ml serum. With the help of high-pressure liquid chromatography (HPLC), the concentration of fluconazole in each of the samples was determine. If the aqueous humor was removed at least 2h after fluconazole application, concentrations between 2.7 and 5.4 micrograms/ml were reached (mean 3.7 +/- 2.17) In these cases the concentration in the aqueous humor was 80% of the concentration found in the serum at the same time. If the sample of the aqueous humor was collected only 1 h after application, 40% of the concentration in the serum was found in the aqueous humor. These data prove that fluconazole shows an extremely good penetration through the blood-aqueous barrier. After a single dose of 200 mg, a concentration is reached in the eye that surmounts the minimal inhibiting concentration found for Candida species sensitive to fluconazole. Therefore, fluconazole seems to be a good alternative to amphotericin B for the treatment of infections caused by such fungi.

Administration, Oral↗
PubMedDate not supplied

Elevation of atrial natriuretic peptide levels in aqueous humor of the rabbit by kappa opioid receptor agonists.

Following the topical administration of three kappa agonists (bremazocine, spiradoline and ICI 204448) to rabbit eyes, aqueous humor samples were analyzed for levels of atrial natriuretic peptide (ANP). Bremazocine (BRE) and spiradoline (SPR) elevated aqueous ANP levels in a dose-dependent manner. In contrast, ICI had no significant effect on ANP levels in aqueous humor. Nor-binaltorphimine (nor-BNI), a selective kappa opioid receptor antagonist, was used to assess kappa opioid receptor involvement and glibenclamide, an ATP-sensitive K+ channel blocker, was used to test for the role of ATP-sensitive potassium channels in ANP release. Pretreatment with nor-BNI antagonized the increases in ANP levels observed with both BRE and SPR. Likewise, glibenclamide suppressed the stimulation of ANP secretion by bremazocine. In summary, BRE and SPR increased ANP levels in aqueous humor of rabbits, in part, via activation of K+(ATP) channels that are assumed to be associated with kappa opioid receptors.

Analgesics↗
PubMed2000

Capillary electrophoretic analysis of brimonidine in aqueous humor of the eye and blood sera and relation of its levels with intraocular pressure.

The aim of this study was the development of a capillary electrophoretic method for the determination of the levels of the selective alpha(2)-adrenergic receptor agonist brimonidine in aqueous humor of the eye and blood sera and their relation to its efficacy in reducing the intraocular pressure (IOP). Analysis of brimonidine was performed by capillary zone electrophoresis using 20 mM borate, pH 9.3, as operating buffer and detection at 255 nm. Brimonidine levels were determined in aqueous humor and blood sera from seven patients admitted for cataract extraction following ocular administration of the ophthalmic Alphagantrade mark solution. Levels of brimonidine and IOP values were recorded for a 24 h period. Alphagantrade mark administration resulted in a significant reduction of IOP, from within 30 min up to 4-5 h, whereafter a stepwise increase was recorded until 24 h, where mean IOP value returned to that before administration. The IOP reduction was related to the levels of brimonidine in aqueous humor, where maximal levels (80-100%) were obtained within 1-3 h. A 50% amount of the solution was determined after 4-5 h, whereas it reached the minimum level after 12 h. Serum levels reached maximum within 3-4 h, a 50% reduction was recorded in 12 h and minimum level in 24 h. It is concluded that brimonidine administration may significantly reduce IOP in patients when its level is maintained >/=50% of the maximum present in aqueous humor, i.e within a 4-6 h period. Since at this time the level of brimonidine in blood serum has reached maximum value, administration of brimonidine every 6 h may be used to obtain adequate brimonidine levels to maintain a constantly lowered IOP.

Adrenergic alpha-Agonists↗
PubMed1991

MK-507 (L-671,152), a topically active carbonic anhydrase inhibitor, reduces aqueous humor production in monkeys.

An investigation was carried out to determine the mechanism by which MK-507 (L-671,152), a water-soluble inhibitor of human carbonic anhydrase II in vitro, reduces intraocular pressure when applied topically to monkey eyes. Intraocular pressure, tonographically measured outflow facility, and fluorophotometrically determined aqueous humor flow were measured before and after therapy in eight normal cynomolgus monkeys. Fifty microliters of 2% MK-507 was instilled in one eye and diluent in the contralateral eye. Baseline values for intraocular pressure, outflow facility, and aqueous humor flow were similar in the drug-treated and diluent-treated control eyes. After therapy, intraocular pressure was significantly (P less than .05) reduced from 1 to 7 hours (eg, 14.0 +/- 1.0 and 15.9 +/- 0.9 mm Hg [mean +/- SEM], treated and control eyes, respectively, at 3 hours). Outflow facility was not significantly (P greater than .40) changed at 3 hours, and aqueous humor flow measured over 5 hours was significantly (P less than .05) reduced (38%) in treated (0.9 +/- 0.1 microL/min) as compared with control eyes (1.5 +/- 0.1 microL/min). The results suggest that MK-507 reduces intraocular pressure by decreasing aqueous humor production.

Administration, Topical↗