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Aqueous humor dynamics in monkeys after topical R-DOI.

PURPOSE: To determine the effects of R-DOI, a selective 5-HT2 agonist, on intraocular pressure (IOP) and aqueous humor dynamics in monkeys. METHODS: Normotensive cynomolgus monkeys (n = 8) were treated topically once daily with four 5-muL drops of 0.5% R-DOI in one eye, vehicle in the opposite eye. The 6-hour IOP response (Goldmann applanation tonometry) was determined before the drug application and on the third day of treatment. Aqueous humor formation, or flow (AHF, measured by fluorophotometry), was measured from hours 3 to 8 after the third dose. Beginning 3.5 hours after the fourth or fifth dose, AHF was measured by dilution of radio-iodinated monkey albumin perfused through the anterior chamber and flow to blood by accumulation of albumin in the general circulation. Uveoscleral outflow (Fu) was calculated. Flow to blood was determined at spontaneous and elevated pressures, allowing calculation of trabecular outflow facility. Total outflow facility was determined by two-level constant pressure perfusion from 3.5 to 5 hours and from 5.5 to 6.25 hours after R-DOI treatment. RESULTS: Reduction of IOP in treated eyes was compared to the opposite control eyes corrected for the 6-hour IOP baseline before the first dose. After the third dose of R-DOI, IOP was significantly (P < 0.01, n = 7) decreased by 1.4 to 4.7 mm Hg over the 6 hours. AHF (by fluorophotometry) increased by 13% (P < 0.05, n = 8) in treated compared with control eyes corrected for baseline. AHF (isotope dilution) increased by 30% (P < 0.01, n = 8), flow to blood decreased by 28% (n = 5), and Fu increased by 241% (P < 0.05, n = 5). Total and trabecular outflow facility were unchanged. CONCLUSIONS: R-DOI caused a small but significant increase in AHF and lowered IOP in normotensive monkeys primarily by increasing Fu.

Administration, Topical↗

[Effects of amosulalol hydrochloride on intraocular pressure and aqueous humor dynamics in the rabbit eye].

The effects of amosulalol, which blocks alpha 1 adrenoceptors selectively and beta receptors nonselectively almost to the same extent, on intraocular pressure (IOP) and aqueous humor dynamics were studied in pigmented rabbits. Administration of topical amosulalol (0.5%) resulted in a significant difference in IOP between the treated and the contralateral eyes from 0.5 to 6 hours, and the maximum IOP reduction, 6.0 +/- 0.4 mmHg (mean +/- standard error), was observed at 2 hours after administration. Aqueous humor dynamics measurements (mean +/- standard error) in the amosulalol (0.5%)-treated and the contralateral eyes revealed that total outflow facility determined by the two-level constant pressure perfusion method was not significantly different, 0.14 +/- 0.01 and 0.12 +/- 0.01 microliter/min/mmHg, respectively; the aqueous flow measurements determined by fluorophotometry were 3.0 +/- 0.1 and 3.4 +/- 0.2 microliters/min, respectively (p < 0.05, -11%); the uveoscleral outflow measurements determined by the fluorescein isothiocyanate-dextran perfusion method were 0.53 +/- 0.04 and 0.46 +/- 0.04 microliter/min, respectively (p < 0.05, +15%). In conclusion, amosulalol lowers the IOP by inhibiting aqueous production and increasing uveoscleral outflow.

Adrenergic alpha-Antagonists↗

A study of aqueous humor dynamics in keratoconus.

Clinical observations suggest that patients with keratoconus have lower intraocular pressures, on average, than normal subjects. Our purpose was to determine whether differences in aqueous production and outflow facility could account for differences in intraocular pressure between a group of patients with keratoconus and a group of normal, age-matched control subjects. Aqueous humor dynamics were determined by the use of fluorophotometry in one eye of seven patients with keratoconus and ten age-matched normal subjects. Intraocular pressure was measured by applanation tonometry. Keratoconus patients had a statistically significant lower mean intraocular pressure than normal control subjects (11.3 +/- 1.6 mmHg vs. 16.6 +/- 2.8 mmHg, P = 0.0004). The difference in mean intraocular pressure remained significant even after correcting for possible errors in applanation tonometry due to thin corneal stroma. There was no difference in mean aqueous humor flow rates in the keratoconus patients as compared to controls (2.29 +/- 0.53 microliter min-1, P = 0.73). The mean apparent outflow facility was 0.21 +/- 0.07 microliter min-1 mmHg-1 for keratoconus patients compared to 0.14 +/- 0.03 microliter min-1 for controls (P = 0.02). Lower mean intraocular pressure in keratoconus patients appears to be due to increased outflow facility as compared to normal subjects.

Adult↗

Retinal detachment with oral dialysis: differences in clinical features between cases with and without photoreceptor outer segments in aqueous humor.

Eighteen patients with retinal detachment due to oral dialysis were divided into two groups on the basis of the presence or absence of photoreceptor outer segments in the aqueous humor, and clinical characteristics were compared to elucidate the underlying factors causing the differences. In the group with the presence of the outer segments, oral dialysis was significantly small in size and had no predilection in location. Retinal detachment was significantly long in duration, flat in height, and involved a wide area including the macula. The visual field defect recovered at a significantly high rate after reattachment of the retina. In the group with the absence of the outer segments in the aqueous humor, oral dialysis was significantly large in size and located predominantly in the temporoinferior quadrant. Retinal detachment was significantly short in duration, and cystic or localized around the oral dialysis.

Adolescent↗

Noninvasive glucose monitoring of the aqueous humor of the eye: Part II. Animal studies and the scleral lens.

We have discussed the nature of a scleral lens that will allow us to follow changes in aqueous humor glucose levels in animals by a method based on optical rotation and a technique described in an earlier paper. We have shown how this lens can be micro-miniaturized and can be used in humans as a non-invasive glucose monitor. We have described preliminary experiments designed to show the correlation between the blood glucose assay (BGA) and the aqueous humor glucose concentration as determined by chemical assay (AGA) and by optical rotation determination (ARD). The last mentioned has been obtained by paracentesis directly into a microcell used in conjunction with instrumentation capable of measuring optical rotations as low as 0.0013 degrees (4.5") corresponding to 20 mg/dl glucose with a sensitivity of 0.0001 degrees (0.36"). The variability among normal rabbits as a function of individuality and diurnal changes is described, and the correlation between AGA and ARD shown to be essentially 1.0. Such rabbits are examined when undergoing very rapid decreases in BGA (insulin treatment) or very rapid increases in BGA (bolus of glucose). The AGA and ARD are shown to lag behind the BGA, and this is discussed in terms of the rate of change of BGA with respect to time and its concomitant change in AGA/ARD as well as a simple procedure that would materially reduce this lag.

Animals↗

Cefoxitin levels in human aqueous humor.

We administered 2 g of cefoxitin to 25 patients before cataract surgery. An additional 23 patients received 500 mg of probenecid 30 minutes before the 2-g doses of cefoxitin. Average aqueous humor levels of 1.54, 3.16, 2.46, 1.22, and 0.82 microgram/ml were achieved at 30 minutes and one, two, four, and six hours, respectively, after the 2-g dose. The addition of probenecid prolonged significant aqueous humor levels. Therapeutic levels against common gram-positive pathogens were consistently achieved at two hours after injection without probenecid and from two to four hours after injection with probenecid. Therapeutic levels effective against Enterobacteriaceae were inconsistent.

Aqueous Humor↗

Complement inhibitors in normal cornea and aqueous humor.

C1 inhibitor, beta 1H and C3b inactivator are important inhibitory proteins that regulate the complement system. These inhibitor proteins were detected by gel double diffusion in eluates from normal corneas, but not in normal aqueous humor. Functional tests of C1 inhibitor and C3b inactivator showed low-to-absent levels of these inhibitory proteins in normal aqueous humor. On the other hand, the mean activities of C1 inhibitor and C3 inactivator in corneas were nearly as high as those in sera, and there were no statistically significant differences between the values. The lower molecular weights of complement inhibitors, relative to other complement components, may account for their higher levels in normal cornea and may tip the balance in favor of inhibition of complement activation in the noninflamed cornea.

Adolescent↗

Specific aqueous humor factors induce activation of regulatory T cells.

PURPOSE: To examine the possibility that aqueous humor-induced regulatory T cells could function in vivo, these T cells were examined for their ability to suppress adoptive transfer of delayed-type hypersensitivity (DTH). To begin to understand the mechanisms by which aqueous humor induces activation of regulatory T cells, alpha-melanocyte stimulating hormone (MSH) and transforming growth factor (TGF)-beta2 were examined for ability to induce regulatory T cells. METHODS: Primed T cells were treated with aqueous humor and assayed for regulatory activity by injecting them intravenously along with DTH-mediating T cells into syngeneic mice. Antigen-pulsed antigen-presenting cells (APCs) were injected into the pinna of the mouse ear, and swelling was measured 24 hours later. Primed T cells were also activated in vitro in the presence of alpha-MSH, TGF-beta1, or TGF-beta2 and were assayed for proliferation and TGF-beta production along with suppressing DTH. RESULTS: Aqueous humor-treated T cells suppressed inflammation mediated by DTH T cells. Maximum regulatory T cell activity was induced when primed T cells were activated in vitro in the presence of alpha-MSH followed 4 hours later with active TGF-beta2. Such T cells proliferated, produced TGF-beta, and suppressed DTH, suggesting that alpha-MSH and TGF-beta2 induce activation of regulatory T cells. No regulatory T cell activity could be induced in the presence of TGF-beta1. CONCLUSIONS: The ocular microenvironment constitutively produces immunoregulatory factors that suppress the induction of inflammatory activity and promotes regulatory T cell activity. Such regulatory T cells can further contribute to maintaining the normal immunosuppressive ocular microenvironment through their ability to suppress activation of other inflammatory T cells.

Adoptive Transfer↗

Effect of chronic epinephrine on aqueous humor flow during the day and during sleep in normal healthy subjects.

Epinephrine 2% drops were administered to one eye and a placebo to the fellow eye twice a day for 2 weeks in 18 normal human volunteers. The circadian rhythm of aqueous humor flow was measured by fluorophotometry. Epinephrine (compared with placebo) had no measurable effect on the rate of aqueous flow or the circadian rhythm of aqueous humor flow. These results suggest either that topical application of epinephrine cannot achieve a sustained effect on the mechanism of aqueous formation compared with endogenous epinephrine or that circulating epinephrine is not the sole or principal hormonal messenger that mediates the circadian rhythm of aqueous flow in humans. An experiment in which epinephrine was administered systemically might clarify this ambiguity.

Aqueous Humor↗

[Antibodies to beta-2 glycoprotein I in serum and aqueous humor of patients with glaucoma and their influence on the static perimetry].

PURPOSE: The evaluation of the relationships between the antibodies anti beta-2 glycoprotein I in serum and aqueous humor of the glaucoma patients to the visual field defects. MATERIAL AND METHODS: 48 persons (38 women and 17 men), aged 30-86 (mean age 70), suffering from glaucoma was examined. There were 19 with POAG, 18 with PACG and 11 with PEXG. All patients have undergone trabeculectomy. In plasma and anterior chamber fluid the level of antibodies to beta-2 glycoprotein I classes IgA and IgG were measured using ELISA method (commercial kits produced by Euroimmun), according to producer's instruction. The visual field defects were examined with Humphrey static perimetry. Statistical analysis was performed using Spearman test. RESULTS: There were no significant correlations between antibodies anti beta-2 glycoprotein I, static perimetry, age and duration of the disease. CONCLUSIONS: There have not been stated any relationships between the static perimetry to antiphospholipid antibodies level in serum and aqueous humor in patients with glaucoma. It is the preliminary communication.

Adult↗

Collagen shield drug delivery: therapeutic concentrations of tobramycin in the rabbit cornea and aqueous humor.

Collagen shields made of porcine collagen were placed in a solution containing tobramycin sulfate (40 or 200 mg/ml) for five minutes, then applied to rabbit eyes. One, four, or eight hours after application, the corneas, aqueous humor samples, and shields were assayed for antibiotic. At all intervals, the concentration of antibiotic in the corneas and aqueous humor samples exceeded the mean inhibitory concentration for tobramycin, as determined for most strains of Pseudomonas. Shields immersed in 200 mg/ml tobramycin produced significantly higher concentrations of antibiotic in the cornea at one hour than subconjunctival injections of tobramycin (20 mg) (P = .0001). Shields immersed in 40 mg/ml tobramycin produced higher, although not significantly higher, concentrations of antibiotic in the cornea at one hour than subconjunctival injections of tobramycin (20 mg) (P = .318). Shields immersed in commercially available tobramycin drops or injectable tobramycin solution (40 mg/ml) caused no epithelial damage visible by slitlamp examination. Collagen shields containing antibiotics can serve as a vehicle for drug delivery and may prove superior to current methods for preoperative and postoperative antibiotic prophylaxis and the initial treatment of bacterial keratitis.

Animals↗

Higher concentration of transforming growth factor-beta in aqueous humor of glaucomatous eyes and diabetic eyes.

PURPOSE: Diabetic retinopathy and glaucoma are the primary causes of acquired blindness. Cytokines including transforming growth factor (TGF)-beta may be involved in these diseases. We therefore collected aqueous humor samples from patients with glaucoma and/or diabetes who were undergoing surgery, and determined the concentration of TGF-beta. METHODS: Aqueous humor samples were collected from 80 patients (84 eyes), including 19 eyes with primary open-angle glaucoma (POAG), 22 eyes with diabetes, and 18 eyes with diabetes complicated with POAG. Twenty-five eyes with cataract served as controls. The concentration of TGF-beta1 or TGF-beta2 was measured by enzyme-linked immunosorbent assay. RESULTS: The concentration of TGF-beta1 was less than 0.1 pg/mL in all of the groups. In contrast to controls who had 1001.4 +/- 444.1 pg/mL, the concentration of total TGF-beta2 in the diabetes group was 1715.6 +/- 882.1 pg/mL, and that in the diabetes complicated with POAG group was 1692.9 +/- 361.9 pg/mL. These were significantly higher than that in controls. In contrast to the controls who had 321.2 +/- 197.9 pg/mL, the concentration of mature TGF-beta2 with POAG was 822.5 +/- 484.4 pg/mL, and that of diabetes complicated with POAG was 1058.9 +/- 648.4 pg/mL. These were significantly higher than that in the controls. The eyes with diabetes complicated with POAG also had a significantly higher concentration than the eyes with diabetes alone. CONCLUSION: Total TGF-beta2 and mature TGF-beta2 in high concentration may correlate with progression of POAG, diabetes, and diabetes complicated with POAG.

Aged↗

Corynanthine and aqueous humor dynamics in rabbits and monkeys.

The effects of corynanthine tartrate, a selective alpha 1-adrenergic receptor antagonist, were studied on intraocular pressure by pneumatonometry, outflow facility by tonography, and aqueous humor flow by fluorophotometry in laboratory animals. Unilateral topical administration of 5% corynanthine significantly lowered mean IOP (+/- SEM) in rabbits for at least six hours, in ten awake monkeys for six hours, and in ten monkeys anesthetized with ketamine for four hours. The maximum effect in awake monkeys occurred two hours after drug administration, from 15.8 +/- 0.5 mm Hg to 12.7 +/- 0.5 mm Hg, with no substantial change in control eyes. No change in outflow facility was demonstrated in 11 monkeys two hours after 5% corynanthine administration. Aqueous humor flow rates did not change in 12 monkeys up to three hours after drug administration. Corynanthine may act by increasing uveoscleral outflow.

Adrenergic alpha-Antagonists↗

Specific antibody levels in the aqueous humor and serum of two distinct populations of patients with ocular toxoplasmosis.

The population of Erechim, Southern Brazil, is characterized by a high incidence of ocular toxoplasmosis, which is presumed to be of acquired origin. We wished to compare the local specific humoral immune response of individuals from this region with that of Swiss patients suffering from the same disease. Paired samples of aqueous humor and serum were withdrawn from 27 Brazilian and 50 Swiss patients presenting consecutively with active ocular toxoplasmosis. The total and specific levels of IgG in each of these were determined. The populations did not differ with respect either to age or sex. The serum levels of total IgG in Brazilian (10.8 g/l) and Swiss patients (11.1 g/l) were similar (p = 0.499), but the aqueous humor ones were higher in the former group (95 vs. 20 mg/l; p = 0.0001). The systemic and local levels of specific IgG were likewise higher in Brazilian patients [206 i.u. vs. 72 i.u. (p = 0.001) and 14 i.u. vs. 4 i.u. (p = 0.005), respectively] and the number of individuals without detectable levels of local specific IgG was correspondingly lower (11% vs. 54%; p = 0.0005). The Goldmann-Witmer coefficient (an index of local specific antibody production) did not differ between Brazilian and Swiss patients (2.1 vs. 0.08, respectively; p = 0.107). Our findings are indicative of a more pronounced uveovascular barrier breakdown in Brazilians than in Swiss patients with active ocular toxoplasmosis. That the systemic and local specific immune response is weaker in Swiss than in Brazilian patients has not been hitherto documented. This finding may reflect differences in the immunological handling of the infection.

Adult↗