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[Effect of the ascorbic acid of the aqueous humor on the lipid peroxidation process in the eye in primary open-angle glaucoma].

Investigations of aqueous humor in primary open-angle glaucoma have shown a change in its normal contents: decreased ascorbic acid in it and increased secondary products of lipid peroxidation. In patients with glaucoma of stages III and IV, a correlative relationship between them is recorded (r = -0.78). It is suggested that in the pathomechanism of increased intraocular pressure in primary glaucoma activation of the process of lipid peroxidation plays a role due to decreased concentration of ascorbic acid in the aqueous humor, being one of the most important components of antioxidative system of the eye.

Aged↗

[Detection of antibodies against Brucella in the aqueous humor using ELISA].

In aqueous bulbi of experimentally against Brucella abortus immunized guinea pigs and rabbits specific antibodies could be detected by ELISA-tests. This first demonstration of brucella antibodies in the aqueous shows that aqueous can be used for serological examinations. For practical use more investigations in experimental animals are necessary, e.g. on kinetics of orbital antibodies absence of interfering factors and biomechanics of proteins in aqueous.

Animals↗

Individual measurements of angiotensin II concentrations in aqueous humor of the eye.

The presence of constituents of the renin-angiotensin system (RAS) in ocular tissues and fluids suggests this system is involved in ocular physiology. Angiotensin II (AngII) is the main biological effector of the system, so we measured AngII in plasma and in aqueous humor of the anterior ocular chamber of patients undergoing cataract extraction. Untreated normotensive patients were compared with arterial hypertensive patients taking either diuretics which stimulate the RAS or angiotensin converting enzyme (ACE) inhibitors which reduce the production of AngII. Plasma levels of AngII were higher in patients on diuretics (5.46 +/- 1.04 fmol/ml; mean +/- SEM) than in untreated cataract patients (2.28 +/- 0.32 fmol/ml, p < 0.02), and were very low with ACE inhibitors (0.51 +/- 0.18 fmol/ml). In aqueous humor, AngII was measurable in 7 of 11 patients on diuretics (median 1.1 fmol/ml), and in 6 of 16 normotensive patients (median < 0.55 fmol/ml), but not in aqueous humor of 4 patients receiving enalapril or captopril. These results demonstrate the presence of AngII in the eye but do not exclude either its sequestration in the eye or local production. The possibility of individual measurements of intraocular AngII will permit more precise determination of its role in future studies.

Aged↗

Aqueous humor dynamics in beagle dogs with caffeine-induced ocular hypertension.

In order to investigate the possible mechanisms for caffeine-induced ocular hypertension, the intraocular pressure (IOP) and the outflow through the trabecular meshwork were measured in beagle dog eyes after dosing with intravenous caffeine (30 mg/kg) alone or in combination with the topical beta-blocker befunolol [applied as 100 microliters of a 1% (w/v) solution] which inhibits aqueous humor formation in the ciliary body. Intravenous injections of caffeine significantly increased the IOP at 0.25 and 1 hr after a single dose. The ocular hypertension recovered within 2 hr following dosing. Over time, there were no differences in the outflow between the caffeine and control groups. The instillation of befunolol lowered outflow and produced ocular hypotension. The levels of the IOP and outflow in dogs treated with caffeine and befunolol in combination were almost the same as those in dogs treated with befunolol alone. Single-dose and combination-dose studies demonstrate that intravenous caffeine increases the IOP in normal beagle dogs possibly by increasing aqueous humor formation and not by the inhibition of aqueous humor drainage through the trabecular meshwork.

Adrenergic beta-Antagonists↗

Levels and activation of matrix metalloproteinases in aqueous humor are elevated in uveitis-related secondary glaucoma.

PURPOSE: To measure the levels of matrix metalloproteinase (MMP)-2 and tissue inhibitors of metalloproteinases (TIMP)-2 and to study the expression pattern and molecular forms of MMP-2, 8, 9, 13, and 14 and TIMP-1 and 2 in aqueous humor samples in cases of uveitis-related secondary glaucoma (USG) with a history of up to 20 years by comparison with primary open-angle glaucoma (POAG) and cataracts. METHODS: 33 aqueous humor samples were collected during intraocular surgery. MMP-2 and TIMP-2 levels were analyzed by enzyme-linked immunosorbent assay. Molecular forms and activation degrees of MMPs and TIMPs were analyzed by Western immunoblotting and zymography. The results were related to the clinical data. RESULTS: Enzyme-linked immunosorbent assay measurements of both MMP-2 and TIMP-2 were statistically significantly increased in the USG samples relative to POAG and cataracts (P=0.002). In Western blotting all the MMPs showed increased expression and conversion to their active forms in USG, whereas in the POAG and cataract samples MMPs were found mainly in their latent forms. MMP-8, 9, 13, and 14 showed statistically significantly elevated expression in USG relative to POAG and cataracts on densitometric scanning of Western blots. On zymography, MMP-2 and 9 activation was significantly enhanced in USG compared with POAG and cataracts. CONCLUSIONS: Increased expression of MMPs and their conversion to active forms is characteristics of the aqueous humor in USG, even with a very long history. This emphasizes the fact that increased MMP expression reflects inflammatory disease activity and is probably associated with the development of USG and its complications. Although intraocular pressure is elevated in both glaucoma types, MMP expression in POAG more closely resembles that in cataracts, and therefore the role of MMPs in USG differs very markedly from that in POAG.

Adolescent↗

[Diffusion of pefloxacin in the aqueous humor and crystalline lens after repeated oral administration in man].

The intraocular penetration of pefloxacin was evaluated in 38 patients undergoing extracapsular cataract extraction. Patients were treated for three days with 400 mg of pefloxacin every twelve hours (the first dose being 800 mg). The mean maximum concentration of pefloxacin reached six hours after the last dose in the aqueous humor was 7.69 +/- 3.50 mg/l and reached twelve hours after the last dose in the lens was 4.59 +/- 3.15 micrograms/g. Antibiotic levels were measured by high performance liquid chromatography. Several doses until plasma steady state were effective in obtaining a higher level than a single dose of 400 mg. The ratio between aqueous humor and serum concentrations ranged between 0.50 and 0.89 (mean 68%). These concentrations in aqueous humor were higher than the MIC90 of pefloxacin for most bacterial pathogens involved in endophthalmitis 24 hours after the last dose.

Administration, Oral↗

Human hepatocyte growth factor (HGF) in the aqueous humor.

Using an enzyme-linked immunosorbent assay, we measured the concentration of hepatocyte growth factor (HGF) in human aqueous humor and serum from 36 eyes of 33 patients and analyzed the relationship between HGF and several parameters of corneal endothelial cells. Aqueous HGF concentrations ranged from 0.020-0.194 ng/mL (average: 0.101 +/- 0.044 ng/mL) and was correlated positively with corneal endothelial cell density (r = 0.343, P = 0.04). The aqueous HGF level did not correlate with other corneal endothelial cell parameters or the serum HGF level. The HGF receptor, c-Met, was found in the corneal endothelial cell membranes. This study suggests that the aqueous humor HGF is a factor which maintains an integrity of corneal endothelial cells.

Aged↗

Serotonin in human aqueous humor.

Circadian rhythms in serotonin metabolism have been observed in the pineal gland and retina, and there is evidence that the levels of serotonin and melatonin in these tissues may mediate events in the brain's sleep-wake cycle and the retina's cycle of disc shedding. Because the ciliary epithelium, which produces aqueous humor, has an embryonic origin similar to that of the retina and the pineal gland, the authors believe that serotonin metabolism might play an analogous role in the regulation of the diurnal cycle of aqueous secretion. As a first step in investigating this hypothesis, they measured serotonin concentrations in the aqueous humor of 34 cataract patients. Using high-performance liquid chromatography (HPLC) with electrochemical detection, a mean serotonin concentration of 52 +/- 11 ng/ml was found. This high concentration implies that serotonin has one or more functions: (1) perhaps it acts as a neurotransmitter and precursor of melatonin; (2) conceivably it is related to aqueous humor dynamics; and (3) in particular, perhaps it affects the circadian rhythm of intraocular pressure.

Adult↗

Effect of 8-iso prostaglandin E2 on aqueous humor dynamics in monkeys.

OBJECTIVE: To evaluate the effects of 8-iso prostaglandin E2 (8-iso PGE2; prosta-5,13-dien-1-oic acid,11,15-dihydroxy-9-oxo-,[5Z,8beta-11X,13E,15 S]-) on the intraocular pressure (IOP), outflow facility, and aqueous humor flow rates in normal monkeys and monkeys with glaucoma. METHODS: The IOP was measured before and as long as 6 hours after the topical application of 8-iso PGE2 to 1 eye of 6 normal monkeys and to the glaucomatous eye of 8 monkeys with unilateral laser-induced glaucoma. The pupil diameter was measured at the same times as the IOP measurements in the normal monkeys. Tonographic outflow facility and fluorophotometric flow rates of aqueous humor were measured in 6 normal monkeys before and after drug treatment. RESULTS: In normal monkeys, a single dose of 0.1% 8-iso PGE2 reduced (P<.01) the IOP for 4 hours in the treated eyes with a maximum (mean +/- SEM) reduction of 3.2 +/- 0.2 mm Hg, compared with the contralateral control eyes. The pupil size was smaller (P<.01) in the treated eyes by as much as 1.0 +/- 0.2 mm for 4 hours. In 8 glaucomatous monkey eyes, the application of 0.05% and 0.1% 8-iso PGE2 reduced the IOP (P<.01) for as long as 2 and 5 hours, respectively. The maximum reduction in the IOP was 4.6 +/- 0.8 mm Hg (0.05%) and 6.0 +/- 0.8 mm Hg (0.1%) compared with baseline measurements. The magnitude and duration of the ocular hypotensive effect were enhanced with twice-a-day administration for 5 consecutive days. Outflow facility in normal monkey eyes was increased (P<.05) by 48% in the treated eyes, and aqueous humor flow was unchanged (P>.10), compared with vehicle-treated contralateral control eyes. Mild eyelid edema, conjunctival edema, hyperemia, and discharge appeared in some eyes treated with the 0.1% drug concentration. CONCLUSIONS: The use of 8-iso PGE2 reduces the IOP in both normal and glaucomatous monkey eyes. An increase in outflow facility appears to account for most of the IOP reduction in normal monkeys. CLINICAL RELEVANCE: The application of 8-iso PGE2 may have potential for the treatment of glaucoma as an outflow facility-increasing drug.

Administration, Topical↗

Thrombospondin-1, a natural inhibitor of angiogenesis, is present in vitreous and aqueous humor and is modulated by hyperglycemia.

Negative regulators of angiogenesis play a major role in maintaining vascular homeostasis. Thrombospondin-1 (TSP1) is a natural inhibitor of angiogenesis. This report examines the presence of TSP1 in ocular samples and determines whether its production is altered in diabetes. Western blot analysis detected a 140 kDa antiangiogenic fragment of TSP1(gp140) in vitreous samples prepared from normal human and rat eyes. Intact TSP1 was detected in aqueous humor samples prepared from normal rat and bovine eyes. In contrast, TSP1 was virtually absent in vitreous and aqueous humor samples prepared from diabetic rat eyes. Furthermore, production of TSP1 by microvascular endothelial cells in culture was sensitive to high concentrations of glucose. Retinal blood vessels appeared nonuniform and dilated in diabetic animals when compared to control animals. These results demonstrate that TSP1 and its antiangiogenic fragment are present in aqueous humor and vitreous of normal rat eyes and are dramatically reduced in diabetes. Thus, TSP1 may play a role in ocular vascular homeostasis and its absence may contribute to vascular dysfunctions associated with diabetes.

Animals↗

Penetration of topical cyclosporine into the rabbit cornea, aqueous humor, and serum.

Systemic and ocular absorption of topically applied 10% cyclosporine ointment was determined in rabbit cornea, aqueous humor, and serum by radioimmunoassay. The concentration of the drug in the cornea reached a peak of 900 ng/mL three hours after application. Substantial levels were still present at 24 hours. Relatively low concentrations were measured in the aqueous humor and serum, suggesting corneal stromal pooling of this hydrophobic cyclic peptide. Topical ocular application of cyclosporine may reduce or eliminate the drug's systemic toxic effects while maintaining a therapeutic level of local immunosuppressive activity.

Absorption↗

Effect of vitamin E on glutathione content in red blood cells, aqueous humor and lens of humans and other species.

High doses of orally administered vitamin E have been given to humans, rabbits and rats. Placebo has been given to control groups. At the end of the treatment period, enhanced levels of reduced glutathione (GSH) were found in the red blood cells (humans and rabbits), aqueous humor (humans and rabbits) and lens (rabbits and rats) of treated subjects and animals. The percentage of GSH converted to oxidized glutathione (GSSG) was the same in both vitamin E-supplied and control groups. The GSSG--GSH ratio remained unchanged. The plasma levels of vitamin E were significantly higher in treated than in control subjects and animals. At the end of the study, the levels of vitamin E in aqueous humor and lens of rabbit were the same in animals which received vitamin E and in animals which received placebo. Lastly, vitamin E administration did not influence ascorbic-acid levels in plasma (humans and rabbits), aqueous humor, lens and vitreous body (rabbits).

Animals↗

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

OBJECTIVE: To compare the efficacy of topical 2% dorzolamide hydrochloride (Trusopt) as a suppressor of aqueous humor flow in the human eye with the efficacy of systemically administered acetazolamide (Diamox). DESIGN: A randomized, double-masked, placebo-controlled study of 40 human subjects in 2 academic centers. The effect of dorzolamide on aqueous humor flow was compared with that of acetazolamide as measured by the rate of clearance of topically applied fluorescein. RESULTS: Acetazolamide reduced aqueous flow from 3.18 +/- 0.70 (mean +/- SD) to 2.23 +/- 0.48 microL per minute, a reduction of 30% (P < .001), and dorzolamide reduced the flow to 2.65 +/- 0.64 microL per minute, a reduction of 17% (P < .001). The difference between the effect of acetazolamine and dorzolamide was significant (P < .001). When acetazolamide is added to dorzolamide, the aqueous flow was reduced further to 2.21 +/- 0.47 microL per minute, an additional reduction of 16% (P < .001). When dorzolamide was added to acetazolamide, no additional reduction was observed (P = .73). Similar effects were observed for intraocular pressure. Acetazolamide reduced pressure from 12.5 +/- 2.2 (mean +/- SD) to 10.1 +/- 2.2 mm Hg, a decrease of 19% (P < .001) and dorzolamide reduced it to 10.8 +/- 2.1 mm Hg, or a decrease of 13% (P < .001). The greater effect of acetazolamide than dorzolamide was significant (P = .03). CONCLUSIONS: For reasons that are not known, the topically applied carbonic anhydrase inhibitor 2% dorzolamide hydrochloride is not as effective as systemically administered acetazolamide. Clinicians who prescribe dorzolamide should expect less of an ocular hypotensive effect than that experienced from systemically administered acetazolamide.

Acetazolamide↗

Multiple dosing of prostaglandin F2 alpha or epinephrine on cynomolgus monkey eyes. II. Slit-lamp biomicroscopy, aqueous humor analysis, and fluorescein angiography.

Prostaglandin (PG) F2 alpha (250 micrograms in 50 microliters saline) or epinephrine 2% solution (50 microliters) was topically applied twice daily for 2 weeks to one eye of six cynomolgus monkeys for each agent. Contralateral control eyes received their respective vehicles. A trace aqueous humor flare response occurred in some PGF2 alpha-treated eyes, which reached significance (P less than 0.05) only when observed 4 hr after the first or seventh dose. No significant anterior chamber cellular response was observed in treated as compared to control eyes. Slit-lamp biomicroscopic evaluation of the cornea, iris, and lens showed no differences in treated as compared to control eyes throughout the study. Aqueous humor samples were obtained from all eyes 4 hr after the ninth consecutive dose. Soluble protein concentration was significantly (P less than 0.01) greater in the PGF2 alpha-treated eyes (1.22 +/- 0.30 mg/ml) as compared to control (0.56 +/- 0.17 mg/ml) or to epinephrine-treated eyes (0.59 +/- 0.18 mg/ml). Microscopic examination of sediments obtained after centrifugation of the aqueous humor revealed no cells in experimental or control samples. Both PGF2 alpha and PGE2 levels were significantly (P less than 0.025) greater in PGF2 alpha-treated eyes, and showed a trend towards being greater in epinephrine-treated compared to control eyes. Neither cystoid macular edema nor other retinal abnormalities were evident by fluorescein angiography in any eyes during the second week of treatment. Multiple dosing of PGF2 alpha in monkey eyes does not appear to produce clinically significant adverse effects in either the anterior or posterior segment which would contraindicate its use in a multiple-dose clinical trial in glaucoma patients.

Animals↗