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PubMedDate not supplied

Aqueous humor adrenomedullin levels differ in patients with different types of glaucoma.

PURPOSE: Adrenomedullin is a multifunctional 52 amino acid large peptide. Recent studies have reported that it is expressed in the iris-ciliary body in the eye and that it decreases intraocular pressure (IOP) by increasing outflow facility via specific adrenomedullin receptors, suggesting a role for this peptide in controlling IOP. In the present study, we aimed to explore clinically the possible involvement of adrenomedullin in the pathophysiology of glaucoma. METHODS: Reverse-phase high-performance liquid chromatography was used to determine the aqueous humor adrenomedullin levels in 41 patients (41 eyes) undergoing elective surgery for a variety of ocular diseases in the Research Hospital of Inönü University Medical Faculty between 1999 and 2000. The ocular diseases of the patients included primary open-angle glaucoma (POAG, n = 16), neovascular glaucoma (NG, n = 11), and cataract (n = 14). The study was an open trial with purposive sampling. Aqueous humor samples were taken by paracentesis. Mann-Whitney U-test was used in the statistical analysis and P <.05 was considered as significant. Results were expressed as mean +/- SE. RESULTS: The mean age and sex distribution between groups were comparable. Mean adrenomedullin levels in patients with POAG (22.3 +/- 0.6 pmol/L) were significantly higher than those in patients with NG (5.6 +/- 0.2, pmol/L; P <.001) and cataract (11.9 +/- 0.5, pmol/L; P <.001). On the other hand, the mean aqueous humor adrenomedullin levels in patients with NG were significantly (P <.001) lower than those in cataract patients. CONCLUSIONS: This first clinical in vivo study on aqueous humor adrenomedullin levels showed that this peptide may be involved in the pathophysiology of glaucoma. Increased aqueous humor adrenomedullin levels in patients with POAG may indicate a compensatory defense response against increased IOP to slow the formation and progression of a vicious cycle. On the other hand, there may be deficient production of the peptide in patients with NG, or adrenomedullin-producing cells may be lost because of very high IOP during the course of the disease. The control of adrenomedullin levels in the eye might be a target that could be considered in the therapeutic strategies for glaucoma. Further studies in this respect are needed.

Adrenomedullin↗
PubMed2002

Effects of topical natural ergot alkaloids on intraocular pressure and aqueous humor dynamics in ocular normotensive rabbits.

Although it has been suggested that ergot derivatives may play a role in antiglaucoma therapy, little attention has been paid to the ocular hypotensive action of these drugs. Having previously reported in our laboratory that topical dihydroergocristine decreases intraocular pressure both in ocular normotensive and alpha-chymotrypsin-induced ocular hypertensive rabbits, the aim of the present work was to assess the effect of natural ergot alkaloids, ergocristine, alpha-ergocryptine and ergocornine, on the intraocular pressure and aqueous humor dynamics in ocular normotensive rabbits in order to further explore the ocular actions of these compounds. Intraocular pressure was measured with a pneumatonometer manometrically calibrated for the rabbit eye. Changes in tonographic facility of aqueous humor outflow and rate of aqueous humor inflow were evaluated in anesthetized rabbits. Natural ergot alkaloids were found to reduce intraocular pressure in ocular normotensive eyes in a dose-related fashion. These compounds decreased both tonographic outflow facility and, to a greater extent, aqueous humor inflow, which explains their final hypotensive effect.

Administration, Topical↗
PubMed1985

Human aqueous humor catecholamines.

Timolol of 0.5% was applied in 6 eyes prior to cataract extraction, while 7 eyes were not treated. Aqueous humor was drawn after retrobulbar analgesia with 2% lidocaine and analyzed for epinephrine and norepinephrine using a radioenzymatic assay. Epinephrine levels averaged 15.8 +/- 16.2 and 19.3 +/- 27.5 pg/ml in the timolol treated group and controls respectively. The corresponding values for norepinephrine were 1.59 +/- 0.55 and 1.87 +/- 0.90 ng/ml. These differences were not statistically significant. Norepinephrine levels in this study were somewhat higher than in previous reports of catecholamine levels in human aqueous humor and considerably higher than plasma levels of norepinephrine. There was no significant correlation between aqueous humor norepinephrine levels and age in the two groups combined. The mean norepinephrine levels for men and women in the two groups combined were 1.73 +/- 0.89 and 1.76 +/- 0.56 ng/ml. The difference was not statistically significant. Timolol resulted in a decrease in the intraocular pressure.

Aged↗
PubMed1986

The effect of corticosteroids or nitrogen mustard on aqueous humor chemotactic activity induced by intravitreal endotoxin.

In rabbits intravitreal injection of endotoxin induces potent chemotactic activity for monocytes in aqueous humor. We have assessed the effect of methylprednisolone (30 mg/kg intramuscularly) or nitrogen mustard (1.75 mg/kg intravenously) on the generation of this chemotactic activity. Histologic changes, anterior chamber protein extravasation, and aqueous humor cellular infiltration were reduced by corticosteroids to a variable degree. However, even in animals with a marked reduction in protein extravasation or histologic change, chemotactic activity was substantially preserved. Similarly, nitrogen mustard induced a leukopenia without affecting the ability of endotoxin to generate chemotactic activity in aqueous humor. In contrast, corticosteroids reduced both protein extravasation and the generation of chemotactic activity induced by intravenously injected endotoxin. The results suggest that the chemotactic activity induced in the eye by intravitreal endotoxin may be locally synthesized and may be present without a substantial leukocytic infiltrate.

Animals↗
PubMed1998

Uric acid in the aqueous humor and tears of retinoblastoma patients.

PURPOSE: Malignancy can be associated with high levels of catabolic products. We performed a two-part study. Part 1 measured levels of uric acid and xanthine in the aqueous humor of eyes with malignant and nonmalignant diagnoses. Part 2 measured the levels of uric acid in tears of retinoblastoma patients. If compounds in high concentrations inside the eye could be detected outside the eye, via diffusion, in high concentrations in the tears, then a tear screening test for retinoblastoma could be developed. METHODS: High-performance liquid chromatography measured levels of uric acid and xanthine in aqueous humor samples of patients with retinoblastoma, melanoma, Coats' disease, adult cataract, and congenital cataract. Tear sampling was performed on patients with retinoblastoma and on normal eyes, and samples were assayed for uric acid. RESULTS: Part 1--Uric acid was elevated in the aqueous humor of eyes with retinoblastoma, melanoma, and Coats' disease compared with eyes with cataracts. Xanthine was elevated in retinoblastoma and Coats' disease and was lower in adult and congenital cataracts and melanoma. Part 2-No significant difference was found in the concentrations of uric acid in the tears of patients with retinoblastoma and those of normal patients. CONCLUSIONS: High levels of uric acid and xanthine present in the aqueous humor of patients with malignancy are consistent with the destructive nature of these conditions. Although uric acid was not elevated in the tears of retinoblastoma patients, continued investigation into substances that might be measurably different in the tears may yield a useful screening test in the future.

Adult↗
PubMed2000

[Direct measurement of nitric oxide levels in aqueous humor with selective iso-NO electrode under physiologic conditions and after extracapsular cataract extraction and artificial lens implantation with PMMA in experiments with rabbits].

PURPOSE: To estimate the level of the nitric oxide (NO) within the aqueous humor of the rabbit eye after ECCE and PMMA artificial lens implantation using selective, nitric oxide sensitive electrode Iso-NO. We analysed the NO level during early postoperative period between the 1st and the 5th day. MATERIAL AND METHODS: We examined 30 gray rabbits (weighing 3.0-3.5 kg). Just before surgery, samples of aqueous humor were aspirated to control the NO level in physiological condition. Lens was extracted with ECCE (envelope) technique. In 15 eyes PMMA IOL were implanted and 15 eyes were left aphacic. The aqueous samples were also collected 1, 3, 5 days after surgery. Nitric oxide in each sample was estimated directly with selective, nitric oxide sensitive electrode Iso-NO. Changing values of the NO concentration during the examination were expressed using evaluation of field under curve in the absolute values. Such results were compared with control group. RESULTS: During physiological conditions the mean value of the field under curve of the NO concentration was estimated as 4987.29 +/- 895.89. After ECCE with or without PMMA artificial lens implantation the levels of the NO were higher as compared to the control group. After ECCE and PMMA artificial lens implantation the highest level of NO was estimated on the 3rd postoperative day (7978.98 +/- 949.77). During the examinations the fields under curve of NO concentration were estimated as 6626.30 +/- 1176.53 and 6288.19 +/- 604.90 (on the 1st and the 5th days, respectively). On all postoperative days, values of the field under curve of NO were significantly higher as compared to the control group. In contrast, after ECCE without lens implantation the highest value of NO field under curve, was estimated on the 1st postoperative day as 11727.83 +/- 1032.44. During the examinations, the fields under curve of NO concentration were estimated as 9841.52 +/- 698.06 and 5446.96 +/- 568.47 (on the 3rd and the 5th postoperative days, respectively). Moreover, on all days of examination the value of NO fields under curve were significantly higher as compared to the control group. CONCLUSION: The level of nitric oxide in aqueous humor after ECCE with or without artificial lens implantation was higher than in the control group. The highest value of the field under curve was estimated on the 3rd postoperative day after ECCE and PMMA artificial lens implantation and on the 1st postoperative day after ECCE without lens implantation. The use of direct selective electrode Iso-NO is a simple method of nitric oxide estimation in aqueous humor, but the interpretation of results seems to be very difficult. This method may be suitable for comparative estimations of NO during the experimental works.

Animals↗
PubMed2003

Capillary high-performance liquid chromatographic determination of lutein and zeaxanthin in aqueous humor from a single mouse eye.

To protect the eye from ultraviolet phototoxicity caused by free radicals, ocular components such as the aqueous humor accumulate antioxidants, such as the carotenoids. Lutein and zeaxanthin are the only carotenoids known to be present in the aqueous humor. Due to the small sample volume, pooling of samples from an undesirable large number of animals is often required for sufficient sensitivity and statistically significant differences to be achieved. In this paper we present a rapid, sensitive and robust packed capillary high-performance liquid chromatographic visible detection method for the quantification of lutein and zeaxanthin in the aqueous humor of single mouse eyes.

Animals↗
PubMed1999

An experimental study of the tumour necrosis factor levels in aqueous humor after traumatic cataract and intraocular lens implantation.

PURPOSE: This paper studies the tumour necrosis factor (TNF) levels in aqueous humor after traumatic cataract extraction and posterior chamber (PC) intraocular lens (IOL) implantation in rabbits, and discusses the effect of TNF on postoperative anterior ocular inflammation. METHODS: Twenty-seven pigmented rabbits were divided into three groups: for the first group, the IOL were placed in the capsular bag after traumatic cataract extraction; for the second, the Extracapsular cataract extraction without IOL implantation; and for the third, the control group without surgical intervention. On the 1st, 3rd, 7th and 14th day postoperatively, aqueous humor samples were obtained. A modified double antibodies indirect sandwich ELISA was used to detected for the presence of TNF. The data were studied by means of analysis of variance in SAS software. RESULT: The TNF level was increased in aqueous humor and reached its maximum on the 1st postoperative days after traumatic cataract extraction and PC IOLs implantation, and the TNF levels are significantly higher (P<0.05) on the 1st, 3rd, 7th and 14th day postoperatively in traumatic cataract extraction and PC IOL implanted group than that in the non-surgical-intervention group and extracapsular cataract extraction group. CONCLUSIONS: The increase of TNF levels had a close relationship with presence of the IOL itself which induces the secretion of TNF. This suggested that TNF as the principal mediators of immunological and inflammatory responses, so that may play critical role in anterior ocular inflammative response after traumatic cataract extraction and IOL implantation.

Animals↗
PubMed2005

Hypophosphorylation of aqueous humor sCD44 and primary open-angle glaucoma.

PURPOSE: The ectodomain of CD44, the principal receptor for hyaluronic acid (HA), is shed as a 32-kDa fragment-soluble CD44 (sCD44)-which is cytotoxic to trabecular meshwork (TM) cells and retinal ganglion cells (RGCs) in culture. The purpose of this study was to characterize sCD44 further by determining the phosphorylation of aqueous humor sCD44 in normal and primary open-angle glaucoma (POAG). METHODS: Aqueous humor samples of patients were subjected to CD44 enzyme-linked immunosorbent assay (ELISA) and two-dimensional (2-D) polyacrylamide gel electrophoresis, followed by Western blot analysis with anti-CD44, anti-serine/threonine, and anti-tyrosine phosphospecific antibodies, to determine sCD44 concentration, isoelectric point (pI), and phosphorylation, respectively. The bioactivity of hypophosphorylated sCD44 was tested in cell culture and HA affinity columns. RESULTS: Two-dimensional Western blot analysis revealed that the representative pI of the 32-kDa sCD44 was 6.96 +/- 0.07 in POAG versus 6.38 +/- 0.08 in normal (P < 0.0004). Enzymatic dephosphorylation of sCD44 resulted in a basic shift in the pI. The normal aqueous humor sCD44 was positive for serine-threonine phosphorylation; however, POAG sCD44 was hypophosphorylated. Hypophosphorylated sCD44 was more toxic to TM and RGC cells than standard sCD44, and hypophosphorylated sCD44 had decreased affinity to HA, particularly with increased pressure. CONCLUSIONS: POAG aqueous is characterized by posttranslational change in the pI of sCD44 and hypophosphorylation, which clearly distinguished POAG from normal aqueous humor. The high toxicity and low HA-binding affinity of hypophosphorylated sCD44 may represent specific pathophysiologic features of the POAG disease process.

Aqueous Humor↗
PubMed2000

Aqueous humor nitric oxide levels differ in patients with different types of glaucoma.

Nitric oxide (NO) has effects on the regulation of aqueous humor dynamics, but the exact mechanism is not yet established. To investigate the possible roles of NO in glaucoma, we determined NO levels in aqueous humor and plasma in glaucoma patients and a control group, cataract patients. The study is an open trial with purposed sampling. One hundred fifty-two patients, including 87 glaucoma patients and 65 cataract patients from two medical centers, were recruited. NO levels in the samples were measured by a chemiluminescence assay. We found that, although the mean aqueous humor NO level (mean +/- SEM) was higher in the glaucoma patients than in the cataract patients (39.7 +/- 1.5 microM vs. 35.5 +/- 1.3 microM, p < 0.05), NO levels varied significantly in different types of glaucoma. The juvenile glaucoma patients had the lowest mean NO level (8.4 +/- 0.9 microM), while the acute angle-closure glaucoma and neovascular glaucoma patients had the highest mean NO levels (64.8 +/- 7.6 microM, 67.3 +/- 8.2 microM). In comparison, the mean plasma NO level in the glaucoma patients was not statistically different from that in the cataract patients (14.1 +/- 1.2 microM vs. 13.9 +/- 1.1 microM, p = 0.91). Our data may provide information for applying NO-mimicking nitrovasodilators in the treatment of glaucoma.

Aged↗
PubMed2001

Effects of serotonergic compounds on aqueous humor dynamics in monkeys.

PURPOSE: The effects of several serotonergic agonists on aqueous humor formation (AHF), total outflow facility (OF) and intraocular pressure (IOP) were investigated in living cynomolgus monkeys. METHODS: We determined the effect of a single topical unilateral 300 microg or 3 mg dose of the 5-HT agonists serotonin, 5-carboxamidotryptamine (5-CT), sumatripan, gepirone, and 8-hydroxy-2(di-n-propylaminotetralin) (8-OH-DPAT) and a 450 microg dose of flesinoxan on IOP (Goldmann applanation tonometry), AHF (scanning ocular fluorophotometry) and total OF (8-OH-DPAT only, topically and intracamerally). RESULTS: Serotonin, 5-CT, sumatripan or gepirone had no significant effect on IOP or AHF. 8-OH-DPAT caused an AHF increase of approximately 70% over 6 hr in both ipsilateral drug- and contralateral vehicle-treated eyes, but no significant change in IOP compared with baseline measured on a separate occasion in the same animals. 8-OH-DPAT did not increase protein levels or rate of entry of systemically administered fluorescein in the anterior chamber aqueous humor compared to historic controls, and no difference was seen between ipsilateral and contralateral eyes. Flesinoxan had no effect on IOP and produced an insignificant 25% increase in flow in treated eyes compared to baseline. CONCLUSION: The results for 8-OH-DPAT and possibly flexinoxan indicate the presence of a secretion-stimulating 5-HT1A receptor in monkey ciliary epithelium that has little effect on IOP. OF was unchanged following 8-OH-DPAT administered topically or following intracameral exchange.

Animals↗
PubMed1978

The penetration of antistaphylococcal antibiotics into the aqueous humor of rabbits.

A multiple dose schedule of antibiotic administration parallels the clinical therapeutic situation. However, most reported studies on the aqueous humor concentration of antibiotics have been carried out following single doses of drug. We administered 2 penicillinase-resistant penicillins, 2 cephalosporins, and gentamicin to rabbits over a 24 hour period. Samples of serum and aqueous humor were obtained after the first and after the fifth dose of antibiotic. Of the agents studied, only methicillin in multiple doses gave therapeutic concentrations in the aqueous humor of normal rabbits. It is proposed that any future studies of intraocular penetration of antimicrobials be designed to include single and multiple doses in normal and infected eyes.

Animals↗
PubMed1979

Experimental ciliochoroidal detachment. Effect on intraocular pressure and aqueous humor flow.

Ciliochoroidal detachments were produced in rhesus monkeys by injecting glutathione bicarbonate Ringer's solution, autologous serum, or silicone oil into the anterior suprachoroidal space. Silicone oil detachments, like sham operations, caused a transient 2 mm Hg reduction in intraocular pressure. Detachments with glutathione bicarbonate Ringer's solution or serum caused a 6 mm Hg reduction in intraocular pressure, which normalized in three weeks. Aqueous humor flow in serum-detached eyes was normal, indicating that the hypotonia does not result from reduced aqueous humor formation. Blood was present in Schlemm's canal in most eyes with hypotonia, which suggests that hypotonia is not the result of enhanced conventional aqueous humor outflow. Therefore, it is postulated that hypotonia might result from enhanced aqueous humor outflow from the anterior chamber into the suprachoroidal space and out of the eye through the emissarial channels of the sclera (uveoscleral outflow).

Animals↗
PubMed1998

Evaluation of microdialysis sampling of aqueous humor for in vivo models of ocular absorption and disposition.

The dynamics of beta-adrenergic-associated reductions in aqueous humor production for treatment of elevated intraocular pressure are not well understood. In particular, the relationship between ocular pharmacokinetics and pharmacodynamics has yet to be established. This study was undertaken to develop a procedure for examining the ocular absorption and disposition of topically administered ophthalmic beta-adrenergic antagonists in individual animals. Dogs were anesthetized with isoflurane and a microdialysis probe was implanted in the anterior chamber of one eye and perfused with 0.9% saline at a rate of 2 microliters min-1. 3H-propranolol was administered by intracameral injection or topically. Each dog received intracameral and topical propranolol, in alternate eyes on separate days, in a randomized cross-over fashion. Microdialysis probe effluent was collected every 5 min for > or = 2.5 h; concentrations of propranolol were determined by liquid scintillation spectroscopy and were corrected for probe recovery of the substrate as determined by in vivo retrodialysis (approximately 46%) to estimate aqueous humor concentrations. In separate experiments in rabbits, microdialysis probes were implanted in each eye. 3H-propranolol was administered topically to one eye; the contralateral eye received intracameral 3H-propranolol. Model-independent pharmacokinetic parameters for each treatment phase were calculated. The mean +/- S.D. times to peak concentration of propranolol in aqueous humor were 86.6 +/- 47.6 min in the dog and 54.1 +/- 20.4 min in the rabbit. The terminal rate constant was 0.0189 +/- 0.00429 min-1 in the dog vs. 0.00983 +/- 0.00546 min-1 in the rabbit. Intraocular tissue availability of propranolol differed markedly between the dog (n = 3) and rabbit (n = 3) (approximately 0.056 in the dog vs. approximately 0.55 in the rabbit). These results demonstrate the utility of microdialysis sampling for examination of ocular pharmacokinetics.

Absorption↗
PubMed1977

Lactate dehydrogenase levels and isoenzyme patterns in the serum and aqueous humor of adult cataract patients.

Serum and aqueous humor lactate dehydrogenase (LDH) levels were assayed in 46 patients with senile cataracts at the time of cataract extraction. The mean aqueous level was 37 IU/liter and the mean serum level 152 IU/liter. In each case, the serum LDH level was higher than the corresponding aqueous LDH. The LDH isoenzyme levels were also determined; LDH 4 and LDH 5 were elevated in cataract aqueous samples, while the serum isoenzymes were normal. The LDH studies of normal and diseased globes must be rigorously standardized to avoid artificially high or low levels.

Adult↗
PubMed1989

Measurement of aqueous humor flow following scleral injection of sulfacetamide as marker: effect of methazolamide, timolol, and pilocarpine.

A simple technique for rapid determination of the flow of aqueous humor (AH) in rabbits is described. Data from control eyes and eyes treated with known inhibitors of aqueous humor production are presented as evidence of the suitability of the technique for comparing the influence of other drugs on aqueous flow. The flow measurement depends on marker dilution by fluid turnover during the first 30 min after 5 microliters marker solution is delivered to the anterior chamber. This is done by passing a needle through the sclera and behind the iris. The advantage of this route is that it permits withdrawal of the needle after delivery without leakage of marker or aqueous humor. Sulfacetamide (SAC), a sulfonamide with low lipid solubility and pKa 5.4, is the marker of flow used here. Control flow data from SAC, fluorescein (FL), reactive blue-2, and 14C-inulin as markers were compared. The control flow measured with SAC in two independent groups is 3.91 and 3.40 microliters/min or 3.69 +/- 0.37 S.E. overall. The data show that inhibition of carbonic anhydrase (CA) in ciliary processes by systemic methazolamide reduces flow 38%. Topical timolol reduces flow 35%. Pilocarpine, which is known to decrease IOP largely by increasing outflow facility, did not significantly reduce flow. This system for measuring AH flow allows rapid accumulation of data for topical, intracameral or systemic treatments.

Animals↗
PubMed1980

[Protein concentrations in the aqueous humor in Coats' disease (author's transl)].

Elevated protein concentrations in the aqueous humor, without Tyndall phenomenon, were found in a case of Coats' Disease. In particular, proteins of smaller size were involved. The permeability of the retinal vessels was presumed to be impaired. The resulting increase in protein concentrations in the aqueous humor could be the cause of the secondary glaucoma in Coats' Disease.

Albumins↗