Abstract Higher expression of reactive oxygen species (ROS) is implicated in neurological disorders. A major event in glaucoma, the death of retinal ganglion cells (RGCs), has been associated with ...elevated levels of glutamate and TNF-α in the RGCs' local microenvironment. Herein we show that the transduction of Peroxiredoxin 6 (PRDX6) attenuates TNF-α- and glutamate-induced RGC death, by limiting ROS and maintaining Ca2+ homeostasis. Immunohistochemical staining of rat retina disclosed the presence of PRDX6 in RGCs, and Western and real-time PCR analysis revealed an abundance of PRDX6 protein and mRNA. RGCs treated with glutamate and/or TNF-α displayed elevated levels of ROS and reduced expression of PRDX6, and underwent apoptosis. A supply of PRDX6 protected RGCs from glutamate and TNF-α induced cytotoxicity by reducing ROS level and NF-κB activation, and limiting increased intracellular Ca2+ influx. Results provide a rationale for use of PRDX6 for blocking ROS-mediated pathophysiology in glaucoma and other neuronal disorders.
Aqueous humor dynamics in the aging human eye Toris, Carol B; Yablonski, Michael E; Wang, Yun-Liang ...
American journal of ophthalmology,
04/1999, Letnik:
127, Številka:
4
Journal Article
Recenzirano
Purpose: Healthy subjects were recruited to identify normal, age-associated changes in intraocular pressure and aqueous humor dynamics.
Methods: Normal healthy subjects from two age groups were ...enrolled in the study: (1) those from 20 to 30 years of age (n = 51) and (2) those 60 years of age and older (n = 53). Intraocular pressure was measured by pneumatonometry, tonographic outflow facility by pneumatonography, and episcleral venous pressure by venomanometry. Aqueous flow and outflow facility were determined by a fluorophotometric technique. Uveoscleral outflow and anterior chamber volume were calculated. Results from the older group were compared with those from the younger group by means of unpaired, two-tailed
t tests.
Results: Compared with the younger group, the older group showed significant differences as follows: smaller anterior chamber volume (160 ± 39 vs 247 ± 39 μl; mean ± SD;
P < .00001), reduced aqueous flow (2.4 ± 0.6 vs 2.8 ± 0.8 μl/minute;
P = .002), and reduced uveoscleral outflow (1.10 ± 0.81 vs 1.52 ± 0.81 μl/minute;
P = .009).
Conclusions: In the healthy aging eye, there is a reduction in the production of aqueous humor and a reduction in its drainage through the uveoscleral outflow pathway.
To report the acute vs chronic effects of brimonidine, a selective alpha2-adrenergic receptor agonist, on aqueous humor dynamics in ocular hypertensive patients.
Brimonidine 0.2% was given topically ...twice daily for 29 days to one eye each of 28 ocular hypertensive volunteers in a randomized double-masked study. The fellow eye was similarly treated with vehicle. Aqueous flow (Fa) and outflow facility (Cfl) were determined with fluorophotometry. Intraocular pressure, outflow facility (Cton), and episcleral venous pressure (Pev) were measured with pneumatonometry, tonography, and venomanometry, respectively. Uveoscleral outflow (Fu) was calculated from intraocular pressure, Fa, Pev, and Cfl values. All measurements were taken on baseline day, day 8, and day 29 of treatment. Intraocular pressure and Fa only were measured after instillation of 1 drop of brimonidine on day 1.
When measured 3 hours after instillation on days 1, 8, and 29 of treatment, brimonidine significantly (P < .001) reduced intraocular pressure by at least 5.0 +/- 0.7 mm Hg (mean +/- SEM) compared with baseline day, and by 2.7 +/- 0.5 mm Hg compared with the vehicle-treated contralateral control eyes. The greatest decrease (6.0 +/- 0.6 mm Hg) was observed at 3 hours after the first drop. Aqueous flow was reduced by 29% (P < .001) after the first application but was not significantly different from baseline when measured at day 29 of treatment. Uveoscleral outflow was increased 60% at day 8 (P < .06) and day 29 (P < .05) compared with baseline. There was no significant difference in outflow facility or episcleral venous pressure at day 8 or day 29 of treatment.
The brimonidine-induced reduction in intraocular pressure in humans is associated initially with a decrease in aqueous flow, and after chronic treatment with an increase in uveoscleral outflow.
On the Nature of Emotion Regulation Campos, Joseph J.; Frankel, Carl B.; Camras, Linda
Child development,
03/2004, Letnik:
75, Številka:
2
Journal Article
Recenzirano
This paper presents a unitary approach to emotion and emotion regulation, building on the excellent points in the lead article by Cole, Martin, and Dennis (this issue), as well as the fine ...commentaries that follow it. It begins by stressing how, in the real world, the processes underlying emotion and emotion regulation appear to be largely one and the same, rendering the value of the distinction largely for the benefit of analysis. There is an extensive discussion of how the same processes can generate emotions (i.e., are constitutive of emotion) and account for variability of manifestation of emotion in context (i.e., regulate them). Following an extensive review of many of the principles involved in emotion and emotion regulation, the paper presents implications for developmental study of infants and children, includes several methodological recommendations, and concludes with an analysis of the extent to which contemporary affective neuroscience contributes to the study of emotion and emotion regulation.
Bimatoprost (Lumigan™ Allergan, Inc, Irvine CA) and travoprost (Travatan™ Alcon, Ft Worth, TX) are two new intraocular pressure (IOP)-lowering drugs for use in patients with glaucoma and ocular ...hypertension. This review evaluates recent studies comparing these new drugs with timolol and with latanoprost. In each study, the statistical analyses support the conclusion that these agents were more effective than timolol and as effective as latanoprost in terms of their ability to reduce IOP. The side effect profiles for bimatoprost, latanoprost, and travoprost were similar, but with statistically higher occurrences of hyperemia and eyelash growth for bimatoprost or travoprost versus latanoprost or timolol.
PURPOSE: To determine the ocular hypotensive mechanism underlying the additivity of latanoprost and pilocarpine.
METHODS: This randomized, double-masked study included 30 patients with ocular ...hypertension on no ocular medications for at least 3 weeks. On each of six visits to the clinic, measurements were taken of aqueous flow and outflow facility by fluorophotometry, intraocular pressure by tonometry, and episcleral venous pressure by venomanometry. Uveoscleral outflow was calculated. Clinic visits were scheduled on baseline day; on day 8 of four times daily pilocarpine (2%) to one eye and vehicle to the other; on day 8 of continued pilocarpine/vehicle treatment plus latanoprost (0.005%) once daily to both eyes; after a 3-week washout period; on day 8 of once-daily latanoprost to one eye and vehicle to the other; and on day 8 of continued latanoprost/vehicle treatment plus pilocarpine four times a day to both eyes. Drug-treated eyes were compared with contralateral vehicle-treated eyes and with baseline day by paired
t tests. Combined pilocarpine and latanoprost–treated eyes were compared with individual drug-treated eyes and with baseline day using the Bonferroni test.
RESULTS: Compared with baseline, pilocarpine reduced intraocular pressure from 18.9 to 16.2 mm Hg (
P = .001) and increased outflow facility from 0.18 to 0.23 μl per minute per mm Hg (
P = .03). No other parameters were affected. Adding latanoprost further reduced intraocular pressure to 13.7 mm Hg (
P < .001) and increased uveoscleral outflow from 0.82 to 1.36 μl per minute (
P = .02). Latanoprost alone reduced intraocular pressure from 17.6 to 14.3 mm Hg (
P < .0001) and increased uveoscleral outflow from 0.89 to 1.25 μl per minute (
P = .05). Adding pilocarpine to the latanoprost treatment further reduced intraocular pressure to 12.7 mm Hg (
P < .001) and increased outflow facility from 0.21 to 0.30 μl per minute per mm Hg (
P = .03).
CONCLUSIONS: Latanoprost and pilocarpine predominantly increase uveoscleral outflow and outflow facility, respectively, when given alone. These drugs are additive because pilocarpine does not inhibit the uveoscleral outflow increase induced by latanoprost.
Anecdotal case reports describe the occurrence of cystoid macular edema, iritis, herpes simplex keratitis, periocular skin darkening, and headaches in patients treated with prostaglandin analogs for ...glaucoma. The purpose of this article is to critically analyze these anecdotal case reports in light of a few well-controlled, randomized clinical studies to determine whether conclusions can be made about a causal relationship between the use of prostaglandin analogs and the occurrence of these side effects. None of these putative side effects has been proven to be causally related to latanoprost therapy using valid scientific methodology. These possible side effects occur rarely. Cystoid macular edema, iritis, and herpes simplex keratitis occur in eyes with risk factors. To scientifically establish a causal relationship between drug therapy and rare side effects, repeated rechallenging with masked controls is required. With rare exception, such methodology has not been used with any of these putative side effects. Nevertheless, even without firm establishment of a causal relationship, caution is advised with the use of prostaglandin analogs in eyes with risk factors for cystoid macular edema, iritis, and herpes simplex keratitis until properly designed, large, controlled studies provide more definitive information.
To determine whether bimatoprost is hydrolyzed to its free acid after topical application in humans in vivo.
Prospective, masked, and vehicle controlled.
Thirty-one eyes of 31 patients with ...cataracts.
Beginning 7 days before scheduled cataract surgery, one eye of each patient was treated with bimatoprost 0.03% or vehicle once daily, with the last drop administered 2 to 12 hours before anterior chamber paracentesis before cataract surgery. In a masked fashion, aqueous humor specimens were assayed for bimatoprost and its free acid by high-pressure liquid chromatography and mass spectrometry.
Detection of the free acid of bimatoprost in aqueous humor.
Aqueous humor concentrations of the free acid of bimatoprost were 22.0±7.0 nmol/l (mean ± standard error of the mean, n = 12) and 7.0±4.6 nmol/l (n = 8) at 2 and 12 hours, respectively, and below the limit of detection after vehicle (n = 10). Concentrations of bimatoprost (amide) were 5.7±1.4 and 1.1±0.4 nmol/l at 2 and 12 hours, respectively, and undetectable after vehicle.
After topical application of bimatoprost in humans, a sufficient concentration of its free acid, a potent FPprostanoid receptor agonist, is found in the aqueous humor to account for its ability to reduce intraocular pressure.
Purpose: The mechanism by which apraclonidine, an α2-adrenergic agonist, lowers intraocular pressure (IOP) was evaluated in humans.
Methods: In a randomized, double-masked, placebo-controlled study, ...0.5% apraclonidine was given topically twice daily for 1 week to one eye in each of 21 ocular hypertensive volunteers. The other eye was treated similarly with vehicle. Before and after 1 week of treatment, aqueous flow, uveoscleral outflow, fluorophotometric outflow facility, intraocular pressure, tonographic outflow facility, episcleral venous pressure, and outflow pressure were either directly measured or mathematically calculated. Values were compared in treated versus contralateral control eyes and on baseline versus day 8 of treatment.
Results: When compared with both contralateral control eyes and baseline day, fluorophotometric outflow facility in the apraclonidine-treated eyes increased by 0.09 to 0.10 μl/minute/mmHg (P < 0.04), IOP decreased by 3.1 to 5.2 mmHg (P < 0.0001), and outflow pressure decreased by 3.3 to 4.2 mmHg (P < 0.0001). When compared with baseline day only, aqueous flow in the apraclonidine-treated eyes decreased by 0.3 μl/minute (P < 0.04), and episcleral venous pressure decreased by 1.0 mmHg (P < 0.001). Episcleral venous pressure also decreased in the control eyes compared with baseline day by 1.3 mmHg (P < 0.001 ). When compared with contralateral control eyes only, uveoscleral outflow in the apraclonidine-treated eyes decreased by 0.47 μl/minute (P < 0.03). Tonographic outflow facility showed no change when compared with either contralateral control eyes or baseline values.
Conclusions: The apraclonidine-induced reduction in intraocular pressure was associated with an increase in fluorophotometric outflow facility, decrease in aqueous flow and decrease in episcleral venous pressure compared to baseline. The lack of a significant difference in aqueous flow and episcleral venous pressure between treated and contralateral control eyes may represent a contralateral drug effect.
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