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PubMed2005

Cl- concentrations of bovine, porcine and ovine aqueous humor are higher than in plasma.

Aqueous humor (AH) Cl- levels were measured from live cows and pigs to confirm the Cl(-)-secretory activities found across the ciliary bodies of these species in in vitro experiments. The values obtained were compared to those of the electrolyte in plasma (PL). In addition, Na+ and K+ concentrations were also measured in AH and PL. For analogy, the same measurements were made in sheep and rabbit. The results indicate that the Cl- AH-to-PL ratios of the bovine, porcine and ovine species, but not that of rabbit, are comparable to published values for humans. Thus, the transport activities of the ciliary epithelia of the former animals may be more adequate as a representative model for human than the commonly used rabbit, which exhibits strikingly different transport properties with a ciliary epithelium that is primarily a bicarbonate-transporting tissue.

Animals↗
PubMed2001

Measurement of the glucose transport time delay between the blood and aqueous humor of the eye for the eventual development of a noninvasive glucose sensor.

In the recent past, several noninvasive optically based methods have been proposed for physiologic glucose sensing. One proposed optical sensing site has been the eye, which, due to its unique optical properties, can be considered as a transparent optical window into the body. In particular, the aqueous humor within the anterior chamber of the eye has been shown to contain glucose levels correlated to those of blood. Concern, however, has been expressed that using the aqueous humor solution as a measure of blood glucose may be problematic due to the potential transport time delay between the blood and the aqueous humor glucose concentrations. This investigation was performed to measure the transport time delay in a rabbit model. The time delay between the blood and aqueous humor glucose concentrations was measured invasively in five New Zealand White rabbits over a series of weeks. An anesthesia protocol containing the drug Xylazine was used to elevate the blood glucose levels to a level commonly seen in diabetic patients. The difference between the glucose peak location times occurring in the blood and aqueous humor glucose response was measured and defined as the transport time delay. The average transport time lag was measured to be under 5 min. This measured time delay indicates that, indeed, the eye could potentially be used as a sensing site for indirect blood glucose measurements and may eventually aid the development of a noninvasive glucose sensor due to its unique optical properties compared to other biological tissues.

Anesthetics, Local↗
PubMed1980

The effect of aqueous humor on the growth of subconjunctival fibroblasts in tissue culture and its implications for glaucoma surgery.

We used aqueous humor from cataract patients and glaucoma patients as a medium for tissue culture of subconjunctival fibroblasts. The aqueous humor from cataract patients consistently inhibited the growth of their own subconjunctival fibroblasts, whereas that of some of the glaucoma patients did not. We found a significant correlation between the success of the filtering operation and the ability of that patient's aqueous humor to inhibit the growth of fibroblasts in tissue culture.

Aqueous Humor↗
PubMed2006

Noladin ether acts on trabecular meshwork cannabinoid (CB1) receptors to enhance aqueous humor outflow facility.

PURPOSE: To study the effects of 2-arachidonyl glyceryl ether (noladin ether), an endocannabinoid ligand selective for cannabinoid (CB)1 receptor, on aqueous humor outflow facility, to investigate the involvement of trabecular meshwork CB1 receptors and the p42/44 MAP kinase signaling pathway and to explore the cellular mechanisms of noladin ether-induced changes of outflow facility. METHODS: The effects of noladin ether on aqueous humor outflow facility were measured in a porcine anterior-segment-perfused organ culture model. The expression of CB1 receptors on cultured porcine trabecular meshwork cells and the coupling of these receptors to p42/44 MAP kinase was determined by immunofluorescence microscopy and Western blot analysis. Both Western blot and zymography were used to monitor the effects of noladin ether on matrix metalloproteinase (MMP)-2. In morphologic studies, AlexaFluor 488-labeled phalloidin staining was used to examine actin filament, and immunohistochemistry with anti-paxillin antibodies was used to detect focal adhesions. RESULTS: Within 1 hour after adding 3, 30, or 300 nM of noladin ether, the aqueous humor outflow facility increased concentration dependently. The effect of 30 nM of noladin ether was completely blocked by SR141716A, a selective CB1 antagonist. Positive signals were detected on cultured porcine trabecular meshwork cells with an anti-CB1 antibody in immunofluorescence microscopy and Western blot studies. Treatment of trabecular meshwork cells with 30 nM of noladin ether activated p42/44 MAP kinase, whereas pretreatment with SR141716A blocked the p42/44 MAP kinase-activating effects of noladin ether. In addition, the enhancement of outflow facility induced by noladin ether was blocked by pretreatment of porcine anterior segments with PD98059, an inhibitor of p42/44 MAP kinase pathway. Furthermore, noladin ether treatment caused rounding of trabecular meshwork cells, and there was a decrease of actin stress fibers, as well as a decrease in focal adhesions. These noladin ether-induced morphologic changes were also blocked by SR141716A and PD98059. CONCLUSIONS: The results demonstrate for the first time that administration of noladin ether, an endocannabinoid agonist selective for the CB1 receptor, increases aqueous humor outflow facility. The data also show that noladin ether-induced enhancement of outflow facility is mediated through the trabecular meshwork CB1 receptor, with an involvement of p42/44 MAP kinase signaling pathway and changes in actin cytoskeletons.

Actins↗
PubMed2001

Effects of topical application of a 2% solution of dorzolamide on intraocular pressure and aqueous humor flow rate in clinically normal dogs.

OBJECTIVE: To evaluate effects of topical application of a 2% solution of dorzolamide on intraocular pressure (IOP) and aqueous humor flow rate in clinically normal dogs. ANIMALS: 15 Beagles. PROCEDURE: The IOP was measured in both eyes of all dogs for 3 days to determine baseline values. In a single-dose study, 50 microl of dorzolamide or control solution was applied in both eyes at 7:00 AM, and IOP was measured 7 times/d. In a multiple-dose study, dorzolamide or control solution was applied to both eyes 3 times/d for 6 days, and IOP was measured 4 times/d during treatment and for 5 days after cessation of treatment. Aqueous humor flow rate was measured for all dogs fluorophotometrically prior to treatment and during the multiple-dose study. RESULTS: In the single-dose study, dorzolamide significantly decreased IOP from 30 minutes to 6 hours after treatment. Mean decrease in IOP during this time span was 3.1 mm Hg (18.2%). Maximal decrease was detected 6 hours after treatment (3.8 mm Hg, 22.5%). In the multiple-dose study, dorzolamide decreased IOP at all time points, and maximal decrease was detected 3 hours after treatment (4.1 mm Hg, 24.3%). Mean aqueous humor flow rate decreased from 5.9 to 3.4 microl/min (43%) after treatment in the dorzolamide group. CONCLUSIONS AND CLINICAL RELEVANCE: Topical application of a 2% solution of dorzolamide significantly decreases IOP and aqueous humor flow rate in clinically normal dogs. Therefore, topical administration of dorzolamide should be considered for the medical management of dogs with glaucoma.

Administration, Topical↗
PubMed1997

Ascorbic acid and amino acid values in the aqueous humor of a patient with Lowe's syndrome.

BACKGROUND: Aminoaciduria is found in Lowe's syndrome. No studies of concentrations of ascorbic acid and amino acids in the aqueous humor of the syndrome have been performed. We examined these concentrations in a patient with Lowe's syndrome. METHODS: Ascorbic acid and amino acid levels in the aqueous humor and plasma of a male infant were measured by means of high-performance liquid chromatography. The patient, who had congenital cataract, miotic pupils, opaque corneas, glaucoma, aminoaciduria, normal levels of ascorbic acid and amino acid in the plasma, and renal tubular acidosis, underwent trabeculotomy, lensectomy, and anterior vitrectomy in both eyes. RESULTS: Intraocular pressure in both eyes decreased to within the normal range, but both corneas remained opaque. The amino acid levels in the aqueous humor were similar to those in the plasma, but intracameral ascorbic acid levels were decreased. After topical instillation of ascorbic acid, the corneas became transparent. The proband's mother had good visual acuity but paracentral lens opacities in both eyes. His maternal grandmother had scattered cortical opacities in both lenses. CONCLUSION: In this infant with Lowe's syndrome, we found intracameral levels of amino acids similar to those in the plasma. Levels of ascorbic acid in the aqueous humor were decreased.

Adolescent↗
PubMed1988

Ciprofloxacin concentration in the rabbit aqueous humor and vitreous following intravenous and subconjunctival administration.

12 mg (6 ml) ciprofloxacin were intravenously administered to rabbits. Using high-pressure-liquid-chromatography the concentration in serum, aqueous humor and vitreous were measured after 1, 4, 10 and 24 h. The mean serum levels were 0.698 mg/l and 0.0425 mg/l after 1 and 10 h, respectively. The drug reached mean levels in the aqueous humor of 0.0595 mg/l and 0.0073 mg/l, respectively. Concerning the subconjunctival application 1 mg (0.5 ml) ciprofloxacin was injected either epibulbar near the limbus corneae or under the conjunctiva of the lower fornix. The mean aqueous humor levels were 0.887 mg/l and 0.094 mg/l after 1 and 10 h, respectively, following epibulbar injection. In contrast, the "fornix-injection" produced mean levels of 0.0267 mg/l and 0.025 mg/l in the aqueous humor after 1 and 10 h, respectively. The concentration of ciprofloxacin in the vitreous was near the detection limit following every method of administration of the drug. The importance of differentiating between epibulbar subconjunctival application and the injection under the conjunctiva of the fornix is discussed.

Animals↗
PubMed1991

The effect of trabeculectomy on the aqueous humor flow of the unoperated fellow eye.

Computerized anterior-chamber fluorophotometry was used to investigate the effect of unilateral antiglaucomatous trabeculectomy on the dynamics of aqueous humor in the unoperated fellow eye. In 14 patients with bilateral primary open-angle glaucoma, pigmentary glaucoma or exfoliation glaucoma, antiglaucomatous trabeculectomy was performed in one eye in which medical management of glaucoma had failed. The fellow eye in all patients had a well-defined history of glaucoma and had been treated with different sorts of medication. The medical management of the unoperated fellow eyes was continued throughout the study. Aqueous humor flow was measured in these eyes prior to surgery and on the 5th day after trabeculectomy. Systemic medication was discontinued from 48 h prior to surgery until second fluorophotometry. The average postoperative flow in the fellow eyes increased from 2.56 to 2.92 microliters/min (P less than 0.05%, paired t-test). The increase in flow in the fellow eyes was independent of topical antiglaucoma medication and of the diurnal rhythm of aqueous humor dynamics. The results of the study indicate that filtration surgery in one eye triggers a CNS-mediated, reflective increase in aqueous flow to maintain physiological stability in the anterior chamber of the surgically treated eye. Since this CNS reflex on aqueous humor dynamics affects both eyes, the clinical observation of intraocular pressure (IOP) dysregulation in the unoperated fellow eye following unilateral trabeculectomy is now understandable.

Adult↗
PubMed1990

Serum and aqueous humor sialic acid levels in Behçet's disease.

Serum and aqueous humor sialic acid (SA) levels were determined in 27 patients with Behçet's disease (Bd). Serum SA levels were elevated significantly during the active episode (mean, 113.4 +/- 4.12 mg/dl) and in the remission stages (mean, 85.4 +/- 4.79 mg/dl; P less than 0.001). A significant increase was also detected in active episodes when compared to chronic stages (P less than 0.02). Aqueous humor levels were also evaluated but could only be determined in the six eyes at the end-stage of the disease (mean, 2.65 +/- 0.60 mg/dl; P less than 0.05).

Acute Disease↗
PubMed2002

Antirecoverin antibody in the aqueous humor of a patient with cancer-associated retinopathy.

PURPOSE: To describe a patient with cancer-associated retinopathy (CAR) in whom antirecoverin antibody was found in the aqueous humor. DESIGN: Interventional case report. METHODS: A 65-year-old man underwent resection of adenocarcinoma of the lung in June 1991 and noted deterioration of vision 10 months later. Goldmann perimetry revealed a ring-like scotoma in each eye, and the electroretinogram was nonrecordable. Aqueous humor and peripheral venous blood were collected for Western blot analysis from this patient and three other patients during surgery for age-related cataract. RESULTS: We found antirecoverin antibody within the aqueous humor and serum in the patient with CAR. In contrast, such imunoreactivities were not observed in specimens from the control patients. CONCLUSION: These observations strongly suggest that antirecoverin antibody penetrates into the aqueous humor and vitreous cavity beyond the blood-retina barrier in CAR.

Adenocarcinoma↗
PubMed1984

Aqueous humor catecholamines.

The catecholamines norepinephrine, (NE) epinephrine (E) and dopamine (DA) were detected for the first time in the aqueous humor of humans under general anesthesia and monkeys under ketamine. The catecholamine levels in aqueous humor of 9 humans were assayed. NE was 0.796 +/- 0.457 ng./ml., E ranged between 0 and 0.132 ng./ml. in 4 out of 9 subjects, and DA was found in 2 of the 9 eyes. (0. 123ng ./ml. and 0. 318ng ./ml..) Plasma levels were measured in 8 of the human subjects at the time of aqueous sampling -NE was 0.311 +/- 0.171, E ranged between 0 and 0.097 (4 out of 8 subjects) and DA was detected in one subject- 0.037 ng./ml.. Monkey aqueous levels were NE:2.843 +/- 0.668 and DA:0.462 +/- 0.177 ng./ml., with an intact iris. (N = 8 eyes.) NE was 0.497 +/- 0.049, and DA 0.426 +/- 0.218 ng./ml. after total iridectomy. (N = 4 eyes) E was not detected in the monkey under these conditions. Whilst NE may be produced in part by the iris, DA levels were not affected by iridectomy. This implies that DA may be produced by structures unrelated to sympathetic nerve endings of the iris in the anterior segment of the non-human primate eye, perhaps by diffusion from the ciliary body or retina. Ketamine is known to inhibit catecholamine uptake, which may explain the high levels measured in the monkey. Human aqueous catecholamine levels measured under anesthesia may be affected by a variety of the drugs used. It is postulated that dopaminergic neurones and associated receptors may be present in the anterior segment of the eye. This may explain the presence of aqueous humor dopamine and the effects of dopaminergic drugs on intraocular pressure.

Adult↗
PubMed2004

Pharmacokinetics of recombinant human basic fibroblast growth factor in rabbits and mice serum and rabbits aqueous humor.

AIM: To study the pharmacokinetics of recombinant human basic fibroblast growth factor (rhbFGF) in rabbits and mice after iv and postocular administration, and the changes of rhbFGF in rabbits aqueous humor after postocular administration. METHODS: After iv or postocular administration three doses of rhbFGF in rabbits and mice, rhbFGF concentration in serum and rabbit aqueous humor was determined by enzyme-linked immunosorbent assay. RESULTS: Serum concentration-time data of rabbits after iv administration of rhbFGF 1, 2, and 4 micro/kg were fitted to bi-exponential equations with half-lives of 0.9, 0.9, and 0.6 min for T1/2alpha and 7, 8, and 4.7 min for T1/2beta. Plasma concentration-time data of mice after iv administration of rhbFGF 2.5, 5 and 10 microg/kg were fitted to bi-exponential equations with half-lives of 0.4, 0.6, and 0.9 min for T1/2alpha and 6, 5, and 7 min for T1/2beta. The AUCs were linearly correlated to doses in both cases (r rabbit=0.997, r mouse=0.999). The serum concentrations of rhbFGF were very low, near to the background after postocular administration of 2 or 5 microg/kg, in both rabbits and mice. The rhbFGF levels in rabbits aqueous humor were higher than control 8 h postdose (P<0.01). CONCLUSION: rhbFGF within the examined doses had a linear pharmacokinetics in rabbits and mice. High concentration of rhbFGF was found in rabbits aqueous humor after postocular administration.

Administration, Topical↗
PubMed2005

Corneal penetration of fluoroquinolones: aqueous humor concentrations after topical application of levofloxacin 0.5% and ofloxacin 0.3% eyedrops.

PURPOSE: To investigate the penetration of topically applied levofloxacin 0.5% and ofloxacin 0.3% eyedrops into the aqueous humor of patients having cataract surgery. SETTING: Hochkreuzklinik Eye Hospital, Bonn, Germany. METHODS: In this randomized, investigator-masked study, 69 patients received 4 drops of either levofloxacin 0.5% or ofloxacin 0.3% eyedrops within 1 hour (60 min, 45 min, 30 min, and 15 min) of elective cataract surgery. Aqueous humor samples of at least 50 muL were drawn from the anterior chamber at the beginning of the cataract operation. The concentrations of the fluoroquinolones in the anterior chambers were measured using high-performance liquid chromatography. To exclude a dilution effect of the anterior chamber (AC), they were related to the AC volumes (measured by 3-dimensional modeling of central Orbscan [Bausch & Lomb] slit-image photos) and AC depths (measured by ultrasound). RESULTS: The mean concentration of levofloxacin (1139.9 ng/mL +/- 717.1 [SD]) in the aqueous humor was significantly higher (P = .0008) than that of ofloxacin (621.7 +/- 368.7 ng/mL). The aqueous humor concentrations correlated negatively with the measured volumes and depths of the ACs. CONCLUSIONS: The new fluoroquinolone, levofloxacin, is more soluble in water enabling the use of higher drug concentrations (0.5%) compared with other currently available fluoroquinolone eyedrops (0.3%). The concentration AC with levofloxacin eyedrops was about 2-fold that reached with ofloxacin eyedrops. The concentration of the antibacterial isomer was approximately 3.5 to 4 times higher when levofloxacin was administered, assuming negligible stereoselective uptake.

Administration, Topical↗
PubMed2005

Absorption of topical moxifloxacin ophthalmic solution into human aqueous humor.

PURPOSE: To investigate the absorption of moxifloxacin into human aqueous humor after administration of moxifloxacin hydrochloride ophthalmic solution, 0.5% as base. METHODS: Cataract patients were randomly allocated to receive 1 drop every 15 minutes for 4 doses before surgery (group 1) or 1 drop 4 times per day on the day before surgery plus the same preoperative regimen as group 1 (group 2). The last dose was administered 0.25, 0.50, 1, 2, or 3 hours before aqueous humor sampling. Samples from 30 patients per group were analyzed by a validated HPLC/MS/MS method. RESULTS: For group 1, the mean +/- SD C(max) was 1.50 +/- 0.75 microg/mL and occurred at 0.5 hour after dosing. The mean C(max) for group 2 was 1.74 +/- 0.66 microg/mL and was reached at 1 to 2 hours. Mean AUC(0-3h) for groups 1 and 2 were 3.16 +/- 0.29 and 4.41 +/- 0.48 microg.h/mL, respectively. The difference in AUC(0-3h) was statistically significant (P = 0.04), but the difference in Cmax was not. CONCLUSIONS: Topical moxifloxacin was well absorbed. Maximum moxifloxacin concentrations were approximately 30 times higher than the median MICs for common pathogens in bacterial endophthalmitis, indicating that either regimen may provide sufficient concentrations to prevent postoperative endophthalmitis.

Absorption↗
PubMed2005

CB2 cannabinoid receptors in trabecular meshwork cells mediate JWH015-induced enhancement of aqueous humor outflow facility.

PURPOSE: To study the effects of JWH015, a CB2-selective agonist, on aqueous humor outflow facility, to investigate whether functional CB2 cannabinoid receptors are expressed in trabecular meshwork cells, and to study whether these receptors are involved in the enhancement of outflow facility induced by JWH015. METHODS: A porcine anterior segment perfused organ culture model was used to measure the effects of JWH015 on aqueous humor outflow facility. Immunofluorescence microscopy, Western blot analysis, and mitogen-activated protein (MAP) kinase activity assays were used to study the expression of CB2 cannabinoid receptors on cultured porcine trabecular meshwork cells and the coupling of these receptors to p42/44 MAP kinase. RESULTS: The outflow facility was increased dose dependently within 1 hour after adding 10, 30, and 100 nM of JWH015, a CB2 agonist. In addition, the effect of 100 nM of JWH015 was completely blocked by SR144528, a selective CB2 antagonist. Furthermore, the outflow-enhancing effect of JWH015 was blocked by pretreatment with PD98059, an inhibitor of the p42/44 MAP kinase pathway. In immunofluorescence microscopy and Western blot studies, positive signals were detected on cultured porcine trabecular meshwork cells with an anti-CB2 antibody. In MAP kinase assays, treatment of porcine trabecular meshwork cells with 100 nM of JWH015 activated p42/44 MAP kinase activity. Pretreatment with SR144528 blocked the effect of JWH015 on p42/44 MAP kinase activity. CONCLUSIONS: The data from this study demonstrate that the CB2-selective cannabinoid agonist JWH015 increases aqueous humor outflow facility. The results also indicate that functional CB2 cannabinoid receptors are expressed in trabecular meshwork cells, and these receptors are involved in the enhancement of outflow facility induced by JWH015.

Animals↗
PubMed2003

Matrix metalloproteinases and their inhibitors in aqueous humor of patients with pseudoexfoliation syndrome/glaucoma and primary open-angle glaucoma.

PURPOSE: To determine the presence, activity, and quantitative differences of matrix metalloproteinases (MMPs) and their endogenous inhibitors (TIMPs) in aqueous humor and serum samples of patients with pseudoexfoliation (PEX) syndrome, PEX glaucoma (PEXG), primary open-angle glaucoma (POAG), and cataract. METHODS: Aqueous humor and serum samples were collected from 100 patients with PEX syndrome, PEX glaucoma (PEXG), POAG, and cataract, respectively. Levels of MMP-1, -2, -3, -7, -9, and -12 and TIMP-1 and -2 were determined by zymography, Western blot analysis, and specific immunoassays. Activity assay kits were used to quantitate levels of endogenously activated MMP-2 and -9. RESULTS: MMP-2, -3, -7, -9, and -12 and TIMP-1 and -2 were identified in human aqueous humor samples from all groups of patients with a six to sevenfold molar excess of TIMPs over MMPs. Whereas serum samples showed no significant differences, total MMP-2 and -3 and TIMP-1 and -2 were detected at significantly higher concentrations in aqueous samples from PEX eyes with and without glaucoma compared with cataractous eyes. MMP-2 and -3 and TIMP-1 were also detected in higher, but not significantly different, amounts in aqueous samples of POAG eyes. However, levels of endogenously activated MMP-2 were significantly decreased in both PEX and POAG samples. The ratio of MMP-2 to its principal inhibitor TIMP-2 was balanced in cataract samples, but was decreased in samples from patients with PEXG, resulting in an excess of TIMP-2 over MMP-2. CONCLUSIONS: The findings suggest that complex changes in the local MMP-TIMP balance and reduced MMP activity in aqueous humor may promote the abnormal matrix accumulation characteristic of PEX syndrome and may be causally involved in the pathogenesis of both PEX glaucoma and POAG.

Aged↗