ascorbic-acid and Ocular-Hypertension

The aim of this work was evaluate the antioxidant effect of ascorbyl laurate (ASC12) based nanostructures applied topically to the cornea of ocular normotensive and hypertensive rabbits. The ASC12 was chosen for its capacity to form liquid lyotropic crystal and keeps its free radical trapping power.. The hypertension model was performed in six rabbits and was obtained by the application of intracameral injections of alpha-chymotrypsin in the right eye. A single 50 ml dose of ascorbyl laurate coagel 2% w/v (COA-ASC12) was applied topically to the cornea of six normotensive and six hypertensive rabbits. The aqueous humor samples were obtained before and after instillation of COA-ASC12 at different times (2 h and 4 h). Antioxidant capacity was determined via the reduction reaction with iron and tripyridyltriazine (FRAP) and the total proteins were measured using the Bradford reagent.. The kinetic antioxidant capacity in the aqueous humor of normotensive and hypertensive rabbits showed a maxim increment at 4 h instillation. Also, the antioxidant capacity in the aqueous humor of hypertensive rabbits was ten times lower than in normotensive rabbits.. This type of nanostructures has the potential to significantly improve the topical formulation for the prophylaxis and treatment of several eye diseases.

Topics: Administration, Ophthalmic; Animals; Antioxidants; Aqueous Humor; Ascorbic Acid; Disease Models, Animal; Gels; Intraocular Pressure; Nanostructures; Ocular Hypertension; Rabbits

The goal of the present study is to establish the antioxidant status in the brain of a high pressure-induced rat model.. Ocular hypertension was induced in rats (n = 12) cauterizing two episcleral veins under a surgical microscope. A sham procedure (n = 12) was performed in the control group. The markers evaluated in the brain 7 days after surgery were as follows: spontaneous chemiluminescence, protein carbonylation, nitrite concentration, total reactive antioxidant potential (TRAP), ascorbic acid, glutathione, vitamin E and activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase.. Chemiluminescence in glaucoma was 55% higher than in controls (393 ± 20 cpm/mg protein, p < 0.001). Protein carbonylation in glaucoma was 93% higher than in controls (1.15 ± 0.18 nmol/mg protein, p < 0.001). Nitrite concentration was 5.30 ± 0.25 μM for glaucoma (controls 4.41 ± 0.24 μM, p < 0.05). Total reactive antioxidant potential decreased by 42% in glaucoma (controls 153 ± 14 μM Trolox, p < 0.001). Ascorbic acid was 67 ± 26 μM for glaucoma (controls 275 ± 22 μM, p < 0.001). Vitamin E was 0.58 ± 0.05 μmol/g organ for glaucoma (controls 1.10 ± 0.06 μmol/g organ, p < 0.01). Glutathione was 1.98 ± 0.13 μmol/g organ for glaucoma (controls 8.19 ± 0.71 μmol/g organ, p < 0.001). Superoxide dismutase and GPx were increased in glaucoma by 42 and 59%, respectively (p < 0.05).. Reactive oxygen and nitrogen species were increased in glaucoma, the increase in chemiluminescence, protein carbonylation and nitrite levels could be evidenced by this situation. The decrease in nonenzymatic antioxidants and a compensatory increase in SOD and GPx activity may have been a consequence of an increase in oxidative processes.

Topics: Animals; Antioxidants; Ascorbic Acid; Brain; Catalase; Disease Models, Animal; Female; Glutathione; Glutathione Peroxidase; Intraocular Pressure; Luminescence; Ocular Hypertension; Oxidative Stress; Protein Carbonylation; Rats; Rats, Wistar; Reactive Nitrogen Species; Reactive Oxygen Species; Superoxide Dismutase; Vitamin E

Pharmacological experiments have suggested that ocular ischemia, induced by high intraocular pressure in the rabbit, provokes an oxidative stress responsible for functional alteration of the retina. However, the nature of the oxidant chemical species and their mode of generation were not elucidated. The aim of the present studies was to characterize the oxygen-derived free radicals produced during and/or after the hyperpressure period. The technique used was based on electron spin resonance spin trapping analysis of the signals obtained in microdialysates of the retina perfused with the nitrone 5-(diethoxyphosphoryl)-5-methyl-1-pyrroline-N-oxide (DEPMPO). The oxidative stress was also evaluated under ischemia and reperfusion periods by measuring the level of ascorbate in the retina via electron spin resonance detection of the ascorbyl free radical-dimethyl sulfoxide (AFR-DMSO) complex. Electroretinograms were recorded to determine the functional consequences of high intraocular pressure and free radical generation. Our results show that superoxide dismutase-inhibitable DEPMPO/hydroxyl radical adducts were generated during the high intraocular pressure period and that the oxidative stress was not increased at reperfusion as assessed by spin trapping and AFR-DMSO measurements. Functional protection provided by free radical scavengers (superoxide dismutase+catalase, TEMPO nitroxide+catalase and dimethylthiourea) against high intraocular pressure-induced electroretinogram alteration confirmed these observations. In conclusion, these experiments demonstrate for the first time by direct measurement that oxygen-derived free radicals are produced by the retina during acute ischemia. This generation could be the explanation for electroretinogram alteration.

Topics: Animals; Ascorbic Acid; Electron Spin Resonance Spectroscopy; Electroretinography; Free Radical Scavengers; Free Radicals; Ischemia; Male; Ocular Hypertension; Rabbits; Reperfusion; Retina; Spin Trapping

Topical application of Iloprost caused a dose-dependent decrease in intraocular pressure (IOP) in rabbits and ocular hypertensive beagles. In rabbits, the IOP response was biphasic and miosis was observed. In beagles, there was no initial hypertensive phase, and the fall in IOP was more pronounced (up to 37%). In beagles, Iloprost did not influence pupillary diameter. A mild transient hyperemia was noted in both rabbit and beagle eyes. Iloprost led to an increase in the aqueous humor protein concentration in rabbits but not in beagles. The use of artificial tears as vehicle enhanced the effect on intraocular pressure but also aqueous protein in rabbits. The central corneal temperature was increased after application of Iloprost in both rabbits and beagles. In rabbits, tonography revealed an increase in outflow facility during both the hypertensive and the hypotensive phases. Iloprost caused a decrease in mean arterial pressure in beagles; the effect on pulse rate was inconsequential. It is suggested that similar low doses of an analog of Iloprost or carboprostacyclin that does not affect the hemodynamic equilibrium could be of value in the treatment of glaucoma.

Topics: Animals; Aqueous Humor; Ascorbic Acid; Blood Pressure; Body Temperature; Conjunctiva; Cornea; Dogs; Dose-Response Relationship, Drug; Epoprostenol; Eye Proteins; Heart Rate; Hyperemia; Iloprost; Intraocular Pressure; Ocular Hypertension; Pupil; Rabbits