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Experimental Eye Research Feb 2013An elevated aqueous humor protein level (aka flare) has always been considered to represent a pathological breakdown of the blood-aqueous barrier (BAB), regardless of...
An elevated aqueous humor protein level (aka flare) has always been considered to represent a pathological breakdown of the blood-aqueous barrier (BAB), regardless of the etiology. Recent studies in humans, using magnetic resonance imaging (MRI) to directly observe BAB kinetics in the posterior chamber of the human eye in-vivo, showed that pilocarpine-induced flare resulting from administration of a single drop of pilocarpine is not the result of breakdown of the BAB in the ciliary body. These MRI studies could not confirm whether pilocarpine caused an increase in iris vascular permeability. In the current studies we completed combined cell-flare meter and intravascular tracer studies, using intravenous horseradish peroxidase (HRP) in rabbits. One hour after receiving 3% pilocarpine in one eye, pupil size significantly decreased and aqueous flare significantly increased in pilocarpine-treated eyes. Light and electron microscopy demonstrated no leakage across either the iris vascular endothelium or the non-pigmented ciliary epithelium in either pilocarpine-treated or control eyes. One animal received HRP directly after pilocarpine to control for a transient increase in permeability before the peak flare response occurred. No leakage was found in the ciliary body or iris of this animal. Additional animals received topical pilocarpine in one eye but after 1 h they were sacrificed without tracer studies. Uveal tissues from these animals were used to assess the distribution of non-HRP protein in the ocular anterior segment and to assess the amount of elutable protein in the iris stromas of both treated and untreated eyes. Immunohistochemistry confirmed the presence of a reservoir of protein in the iris stroma. Analysis of elutable total protein from the iris stroma of pilocarpine-treated and control eyes showed significantly less total elutable protein in pilocarpine-treated eyes. Eyes with the greatest percent change in pupil size (i.e. the strongest miosis) correlated with lowest amounts of residual protein in the iris stroma. The tracer studies confirmed recent MRI studies in humans showing that the source of pilocarpine-induced flare is not disruption of the ciliary epithelial barrier. Extending this work, the current studies also showed no pilocarpine-induced leakage from the iris vasculature. The elutable protein experiments suggested that a primary source of pilocarpine-induced flare was extrusion of a portion of the reservoir of protein in the iris stroma. Taken together, these studies strongly suggest that not all clinically observable flare results from breakdown of the BAB.
Topics: Albumins; Animals; Aqueous Humor; Blood-Aqueous Barrier; Capillary Permeability; Ciliary Body; Eye Proteins; Female; Fluorescent Antibody Technique, Indirect; Horseradish Peroxidase; Iris; Male; Miotics; Pilocarpine; Pupil; Rabbits
PubMed: 23187102
DOI: 10.1016/j.exer.2012.11.003 -
The British Journal of Ophthalmology Oct 1964
Topics: Blindness; Drug Therapy; Geriatrics; Glaucoma; Glaucoma, Angle-Closure; Gonioscopy; Humans; Intraocular Pressure; Iris; Manometry; Ophthalmic Solutions; Physostigmine; Pilocarpine; Surgical Procedures, Operative; Tonometry, Ocular; Vision Tests
PubMed: 14221777
DOI: 10.1136/bjo.48.10.544 -
The British Journal of Ophthalmology Dec 1986
Topics: Aged; Blindness; Female; Humans; Hyphema; Male; Middle Aged; Pilocarpine
PubMed: 3801373
DOI: 10.1136/bjo.70.12.933-a -
Investigative Ophthalmology & Visual... Jun 2021Patients that medicate with antidepressants commonly report dryness of eyes. The cause is often attributed to the anticholinergic properties of the drugs. However,...
PURPOSE
Patients that medicate with antidepressants commonly report dryness of eyes. The cause is often attributed to the anticholinergic properties of the drugs. However, regulation of tear production includes a substantial reflex-evoked component and is regulated via distinct centers in the brain. Further, the anticholinergic component varies greatly among antidepressants with different mechanisms of action. In the current study it was wondered if acute administration of antidepressants can disturb production of tears by affecting the afferent and/or central pathway.
METHODS
Tear production was examined in vivo in anesthetized rats in the presence or absence of the tricyclic antidepressant (TCA) clomipramine or the selective serotonin reuptake inhibitor (SSRI) escitalopram. The reflex-evoked production of tears was measured by challenging the surface of the eye with menthol (0.1 mM) and cholinergic regulation was examined by intravenous injection with the nonselective muscarinic agonist methacholine (1-5 µg/kg).
RESULTS
Acute administration of clomipramine significantly attenuated both reflex-evoked and methacholine-induced tear production. However, escitalopram only attenuated reflex-evoked tear production, while methacholine-induced production of tears remained unaffected.
CONCLUSIONS
This study shows that antidepressants with different mechanisms of action can impair tear production by attenuating reflex-evoked signaling. Further, antimuscarinic actions are verified as a likely cause of lacrimal gland hyposecretion in regard to clomipramine but not escitalopram. Future studies on antidepressants with different selectivity profiles and mechanisms of action are required to further elucidate the mechanisms by which antidepressants affect tear production.
Topics: Animals; Antidepressive Agents; Cholinergic Antagonists; Citalopram; Clomipramine; Dry Eye Syndromes; Evoked Potentials, Visual; Lacrimal Apparatus; Methacholine Chloride; Miotics; Rats; Tears
PubMed: 34096973
DOI: 10.1167/iovs.62.7.8 -
Transactions of the American... 1971
Clinical Trial Comparative Study Randomized Controlled Trial
Topics: Acetylcholine; Carbachol; Cataract Extraction; Clinical Trials as Topic; Humans; Miotics; Ophthalmic Solutions; Time Factors; Tissue Adhesions
PubMed: 4949377
DOI: No ID Found -
The British Journal of Ophthalmology May 1967
Topics: Acetazolamide; Adolescent; Adult; Aged; Cataract; Child; Child, Preschool; Cortisone; Eye Diseases; Eye Injuries; Female; Glaucoma; Humans; Hyphema; Infant; Iritis; Male; Middle Aged; Miotics; Mydriatics; Rest; Vision Tests
PubMed: 6022773
DOI: 10.1136/bjo.51.5.315 -
The British Journal of Ophthalmology Mar 1974
Topics: Abducens Nerve; Child, Preschool; Echothiophate Iodide; Eyeglasses; Fixation, Ocular; Follow-Up Studies; Humans; Infant; Isoflurophate; Methods; Ophthalmoplegia; Prognosis; Strabismus
PubMed: 4834597
DOI: 10.1136/bjo.58.3.240 -
Investigative Ophthalmology & Visual... Nov 2011To investigate the effect of cross-linking treatment on corneal permeability in a live animal model.
PURPOSE
To investigate the effect of cross-linking treatment on corneal permeability in a live animal model.
METHODS
Rabbit eyes were selected at random to be left unoperated or to undergo epithelial debridement with or without treatment consisting of cross-linking (CXL) with riboflavin and ultraviolet-A. Nine eyes received a total dose of 3.6 J/cm² and after epithelial healing the corneas were placed in a two-chamber system for quantification of the diffusion of fluorescein compared with controls. Thirty eyes received a total dose of 5.4 J/cm² and, after epithelial healing, in vivo corneal permeability was quantified as the pupillary response over a 30-minute period to a dose of topical pilocarpine compared with controls.
RESULTS
In the ex vivo assay, the mean permeability coefficient in the CXL group (2.42 × 10⁻⁷) was reduced when compared with the unoperated controls (3.73 × 10⁻⁷; P = 0.007) and to the eyes that received epithelial debridement alone (3.74 × 10⁻⁷; P = 0.01). In the in vivo permeability assay, the change in pupillary diameter at 30 minutes after pilocarpine administration was smaller in the CXL group (-1.9 mm), compared with the epithelial debridement group (-2.6 mm; P < 0.001) and with the unoperated controls (-2.7 mm; P = 0.003).
CONCLUSIONS
Corneal cross-linking with ultraviolet-A and riboflavin results in a statistically significant reduction in corneal permeability. These findings suggest that dosing of topical medications may need to be increased in eyes with a history of CXL to achieve expected therapeutic effects, and they may have implications for the long-term health of the cornea.
Topics: Animals; Collagen; Cornea; Corneal Stroma; Cross-Linking Reagents; Debridement; Female; Fluorescein; Miotics; Permeability; Photosensitizing Agents; Pilocarpine; Pupil; Rabbits; Riboflavin; Spectrometry, Fluorescence; Ultraviolet Rays
PubMed: 22064989
DOI: 10.1167/iovs.11-8155 -
Journal of Visualized Experiments : JoVE Feb 2018Temporal lobe epilepsy (TLE) is a common neurological disorder in adulthood. For translational studies of chronic epilepsy, pilocarpine-induced status epilepticus (SE)...
Temporal lobe epilepsy (TLE) is a common neurological disorder in adulthood. For translational studies of chronic epilepsy, pilocarpine-induced status epilepticus (SE) is frequently selected to recapitulate spontaneous recurrent seizures (SRS). Here we present a protocol of SE induction by intraperitoneal (i.p.) injection of pilocarpine and monitoring of chronic recurring seizures in live animals using a wireless telemetry video and electroencephalogram (EEG) system. We demonstrated notable behavioral changes that need attention after pilocarpine injection and their correlation with hippocampal neuronal loss at 7 days and 6 weeks post-pilocarpine. We also describe the experimental procedures of electrode implantation for video and EEG recording, and analysis of the frequency and duration of chronic recurrent seizures. Finally, we discuss the possible reasons why the expected results are not achieved in each case. This provides a basic overview of modeling chronic epilepsy in mice and guidelines for troubleshooting. We believe this protocol can serve as a baseline for suitable models of chronic epilepsy and epileptogenesis.
Topics: Animals; Disease Models, Animal; Electrodes, Implanted; Electroencephalography; Epilepsy, Temporal Lobe; Male; Mice; Miotics; Pilocarpine
PubMed: 29553531
DOI: 10.3791/56831 -
Acta Pharmaceutica (Zagreb, Croatia) Sep 2009This study is aimed to design and optimize a sublingual tablet formulation of physostigmine salicylate, an effective drug in Alzheimer's disease and nerve gas poisoning,... (Comparative Study)
Comparative Study
This study is aimed to design and optimize a sublingual tablet formulation of physostigmine salicylate, an effective drug in Alzheimer's disease and nerve gas poisoning, by means of the D-optimal experimental design methodology. Polyvinyl pyrrolidone, lactose, starch 1500 and sodium starch glycolate were used in the formulations as independent variables. Tablets were prepared by the direct compression method and evaluated for their physical properties (tablet hardness, disintegration time and friability), which were regarded as responses in a D-optimal design. Due to the significance of the special cubic model for data fitted, compared to other models, it was used to examine the obtained results. Response surface plots were plotted to study the tablet properties and the optimized overlay plot was generated based on the results and targets considered for the responses. After verification of the optimum checkpoint formulations, an optimized formulation was chosen due to its desirable physical properties and closely observed and predicted values. Drug assay, content uniformity of the dosage unit, drug dissolution and accelerated stability studies were done on the optimum formulation as further experiments. All the obtained results complied with the requirements of a sublingual tablet formulation.
Topics: Administration, Sublingual; Chemistry, Pharmaceutical; Drug Stability; Physostigmine; Tablets
PubMed: 19819826
DOI: 10.2478/v10007-009-0028-5