Papers by Ruth Rosenstein
Journal of Neurochemistry, Mar 12, 2020
Optic neuritis, a neuropathy which affects mainly young adults and children, provokes primary inf... more Optic neuritis, a neuropathy which affects mainly young adults and children, provokes primary inflammation, demyelination, and optic nerve axon injury, leading to retinal ganglion cell (RGC) death and visual dysfunction (Aranda,
Study of Radial Optic Neurotomy Outcomes in Normal Rat Eyes
Investigative Ophthalmology & Visual Science, Apr 17, 2010
PubMed, 2012
Glaucoma is a leading cause of blindness worldwide, characterised by specific visual field defect... more Glaucoma is a leading cause of blindness worldwide, characterised by specific visual field defects due to the degeneration of retinal ganglion cells and damage to the optic nerve head (ONH). Elevated intraocular pressure (IOP) is the most important risk factor for glaucoma development. One of the clinical hallmarks of glaucomatous optic neuropathy is the excavation of the ONH, which consists of a progressive posterior displacement of the ONH surface and excavation of the pre-laminar tissues beneath the anterior-most aspect of the scleral canal, known as the anterior scleral ring. Radial optic neurotomy (RON) is a surgical technique that has been proposed for treating central retinal vein occlusion. While the original rationale of RON was the relief of increased tissue pressure within the optic nerve that results from occlusion of the central retinal vein, recent results are discussed here which suggest that by relaxing of the scleral ring of the prelaminar and laminar regions of the ONH, RON may alleviate the IOP-related connective tissue stress, and in turn, prevent the onset and reduce the progression of glaucomatous neuropathy.
Journal of Pineal Research, Apr 1, 1990
In order to analyze whether the bovine pineal gland is a homogeneous or a heterogeneous structure... more In order to analyze whether the bovine pineal gland is a homogeneous or a heterogeneous structure as far as monoamine content, the regional differences in norepinephrine (NE), dopamine (DA), serotonin (5HT), and 5-hydroxyindoleacetic acid (SHIM) contents were assessed by high-pressure liquid chromatography. NE content was maximal in the proximal (close to the recessus pinealis) region and decreased in a rostral-caudal direction to achieve minimal values at the distal region. DA exhibited an opposite trend to NE, NE/DA ratios varying from 3.2 (proximal region) to 1.4 (distal region). Significantly lower NE content was found at the inferior as compared to the superior pineal region, and at the cortex as compared to the medulla. No significant differences were detected in DA concentration of these latter pineal regions, or in 5HT or S H I M concentration as a function of the region examined. 'H-5HT and 'H-NE uptake were maximal at the proximal zone in a rostral-caudal direction, at the superior as compared to the inferior region, and at the medulla as compared to the cortex. Unlabeled NE was equally effective to compete with 'H-5HT uptake in the several pineal regions studied. While NE increased maximally 'H-5HT release in a rostral-caudal direction, DA exhibited an opposite trend, displaying maximal 5HT release activity at the distal pineal region. DA and NE 5HT-releasing activity were greater in the pineal medulla than in the cortex, and did not exhibit differences in the superior as compared to the inferior pineal aspects. Excess (55 mM) K + released 'H-5HT to a similar extent regardless of the pineal region examined.
Release and effect of?-Aminobutyric acid (GABA) on rat pineal melatonin productionin vitro
Cellular and Molecular Neurobiology, Jun 1, 1989
Summary 1.3H-γ-Aminobutyric acid (GABA) release elicited by a depolarizing K+ stimulus or by nora... more Summary 1.3H-γ-Aminobutyric acid (GABA) release elicited by a depolarizing K+ stimulus or by noradrenergic transmitter was examined in rat pinealsin vitro.2.The release of3H-GABA was detectable at a 20 mM K+ concentration in medium and increased steadily up to 80 mM K+.3.In a Ca2+-free medium3H-GABA release elicited by 30 mM K+, but not that elicited by 50 mM K+, became blunted.4.Norepinephrine
Dysregulated light/dark cycle impairs sleep and delays the recovery of patients in intensive care units: A call for action for COVID-19 treatment
Chronobiology International
Journal of Neurochemistry, Oct 1, 2009
Retinal ischemia induces irreversible changes that result in blindness. Ischemic retinopathy deve... more Retinal ischemia induces irreversible changes that result in blindness. Ischemic retinopathy develops when retinal blood flow is insufficient to match the metabolic needs of the retina, one of the highest oxygen-consuming tissues. At cellular level, retinal ischemic injury consists of a self-reinforcing destructive cascade involving several mechanisms, such as depolarization, calcium influx, oxidative stress, and increased glutamatergic stimulation, among others [reviewed by ]. In addition, reperfusion with oxygenated blood after ischemia also has the potential to aggravate ischemic damage, an effect known as reperfusion injury. Although at present there is no effective treatment, it is possible to activate an endogenous protection mechanism that prevents from retinal ischemia/reperfusion (I/R) damage by ischemic pre-conditioning (IPC) . IPC requires a brief period of ischemia applied before ischemic injury, which does not produce any significant damage per se, and triggers yet incompletely described mechanism(s) that result in tolerance to the subsequent severely damaging ischemic event [reviewed by ]. It was shown that IPC affords the retina a greater degree of functional protection against ischemic damage than any known neuroprotective agent . Although IPC confers robust neuroprotection in different in vitro and in vivo models of ischemia, its translational relevance is limited by the fact that the IPC stimulus must be applied 24 or more hours before the onset of harmful ischemia. Another endogenous form of ischemic protection,
Effect of hyaluronic acid on intraocular pressure in rats
PubMed, Jul 1, 2002
Purpose: To study the effect of acute or chronic intracameral injection of hyaluronic acid on int... more Purpose: To study the effect of acute or chronic intracameral injection of hyaluronic acid on intraocular pressure (IOP) in rats. Methods: Acute or chronic injections of hyaluronic acid were performed unilaterally in the rat eye's anterior chamber, whereas the contralateral eye was injected with saline solution. IOP was assessed daily or weekly by a tonometer in conscious rats. IOP was also assessed in both experimental groups at several intervals during the light-dark cycle. Results: A single injection of hyaluronic acid induced an increase of IOP that lasted for 8 days (P < 0.01), whereas its chronic administration during 9 weeks induced a significant and sustained increase in IOP, compared with the eye injected with vehicle (P < 0.01). This hyaluronic acid-induced hypertension was significantly decreased by the application of 1 drop of brimonidine (0.2%), latanoprost (0.005%), or timolol (0.5%). Significant daily variations of IOP were observed in both control and hyaluronic acid-injected eyes, peaking during the dark phase (P < 0.001, ANOVA). Conclusions: These results suggest that the intracameral administration of hyaluronic acid could be a model of ocular hypertension in rats.
Brain Research Bulletin, Aug 1, 1990
M. C. DfAZ AND D. P. CARDINALI. GABA as a presumprive pcmcrine signal in rhe pined gland. Evidenc... more M. C. DfAZ AND D. P. CARDINALI. GABA as a presumprive pcmcrine signal in rhe pined gland. Evidence on nn intrapineal GABAergic system. BRAIN RES BULL 25(2) 339-344. 1990.-CiABA is present in the pineal gland of several mammals, where it is synthesized in situ as well as taken up from the circulation. This article reviews available information suggesting a local, physiological role of pineal GABA. Both the pinealocytes and the glial pineal cells have the capacity to take up GABA from the extracellular space. The GABA synthesizing enzyme glutamic decarboxylase (GAD) is detectable in the pineal gland; in the bovine pineal GAD exhibits "neuronal-like" properties. By employing a specific antibody against GABA, about 15% of pinealocytes gave a positive reaction in bovine pineal glands. After a depolarizing stimulus, GABA was released from bovine and rat pineal glands by both Ca'+-dependent and Ca'+-independent p recesses. By employing neuronal and glial GABA uptake inhibitors, most %GABA release in bovine pineal gland could be attributed to a "neuronal" (presumably pinealocyte) compartment. Several components of the GABA type A receptor supramolecular complex (i.e., GABA binding sites. central-type benzodiazepine binding sites, Cl-ionophore), as well as a minor population of GABA type B receptor sites, were detected in bovine and human pineal glands. In the rat pineals, GABA is released by norepinephrine (NE) acting through alpha,-adrenoceptors. Physiological concentrations of GABA, by its effect on type A receptor sites, impaired NE-induced melatonin release; by acting on GABA type B receptors, it decreased NE release. Another presumable presynaptic effect of GABA (i.e., to augment maximal velocity and to decrease affinity of NE uptake) was mediated by type A receptor sites. It is proposed that pre-and postsynaptic activity of GABA in the pineal does not differ from that found for GABA interneurons in local circuits of the brain. GABA Pineal gland Paracrine relations GABA receptors Benzodiazepine receptors Cl ionophore Glutamic acid decarboxylase Glial uptake Alpha,-adrenoceptors Norepinephtine uptake and release Melatonin release GABAergic interneurons GABA immunohistochemistry
Neurochemistry International, 1990
The pineal gland serves the function of a neuroendocrine transducer converting information about ... more The pineal gland serves the function of a neuroendocrine transducer converting information about day length into the nocturnal release of melatonin. Melatonin acts on the brain, particularly on the hypothalamus, to affect several biological rhythms. By employing autoradiography and 2-[125I]melatonin as a radioligand, the hypothalamic suprachiasmatic nucleus (SCN) and the pars tuberalis of the adenohypophysis have been identified as sites for melatonin binding exhibiting dissociation constants (Kds) in the 10-~0 M range. These sites were also revealed in test-tube binding assays employing crude membrane fractions. Additionally, studies in either membrane or cytosol fractions using tritiated or radioiodinelabelled melatonin indicated location of another population of presumptive melatonin binding sites with Kds in the 10 810 9 M range in several other brain areas, including the hippocampus, cerebral and cerebellar cortexes, as well as the pineal gland. Signal transduction processes for melatonin presumably involve interaction with G proteins to inhibit adenylate cyclase. Also, a decrease of Ca 2+ uptake, stimulation of guanylate cyclase and inhibition of cyclooxygenase occur at 10-" M melatonin concentrations. The time of administration of melatonin is critical for hormone action. In rodents and humans, a major late afternoon-early evening period of sensitivity is found for several central and peripheral effects of melatonin. Results in rats suggest that central synapses employing z-aminobutyric acid (GABA) as an inhibitory transmitter are a target for pineal melatonin activity because: (a) pinealectomy (Px) disrupts circadian rhythmicity of brain GABA and benzodiazepine (BZP) binding ; (b) low doses of melatonin counteract Px-induced modifications of BZP and GABA binding ; (c) chronic melatonin treatment increases brain BZP and GABA binding ; (d) melatonin administration accelerates brain GABA turnover rate ; (e) melatonin increases glutamic acid decarboxylase activity and CI-ion conductance in the medial basal hypothalamus-preoptic area, with maximal activity in the evening. As BZP, melatonin could affect circadian rhythmicity by modifying GABAergic mechanisms in the endogenous oscillator. Additionally, the epileptoid state described after Px and the mild sedation and torpor that follow administration of pharmacological amounts of melatonin can be explained by an effect on central GABAergic circuits.
Study Of Circadian Activity In Patients With Advanced Glaucoma
Investigative Ophthalmology & Visual Science, Apr 22, 2011
Melatonin Prevents Functional and Histological Alterations in an Experimental Model of Glaucoma in Rats
Investigative Ophthalmology & Visual Science, Apr 28, 2009
Journal of Steroid Biochemistry, Jun 1, 1984
The high affinity binding of [3H]flunitrazepam (FNZP) to crude membrane preparations was examined... more The high affinity binding of [3H]flunitrazepam (FNZP) to crude membrane preparations was examined in human pineal glands. Scatchard analysis of the data at equilibrium revealed a single population of binding sites with dissociation constant = 2.36-2.53 nM and binding site concentration= 59-108 fmol/mg protein. When various benzodiazepine (BZP) analogues were tested for their ability to inhibit [3H]FNZP binding the following K i (nM) were found: clonazepam (0.13), RO 15-1788 (0.60), FNZP (2.14), diazepam (13.5), Ro 5-4864 (> 10000). In both human pineal gland and cerebral cortex 10-100 #M y-aminobutyric acid (GABA) increased BZP binding by about 30%, an effect inhibited by the GABA receptor blocker bicuculline. The stimulatory effect of GABA on [ 3 H]FNZP binding in rat cerebral cortex (about 60%) decreased as a function of time elapsed postmortem at room temperature to reach values similar to those observed in human brains. These results suggest the existence of central type BZP receptors in the human pineal glands. Pineal gland Cerebral cortex Benzodiazepine receptors GABA Human
Daily changes in presynaptic cholinergic activity of rat sympathetic superior cervical ganglion
Brain Research, Feb 1, 1994
The in vitro capacity of sympathetic superior cervical ganglia (SCG) to take up [3H]choline from ... more The in vitro capacity of sympathetic superior cervical ganglia (SCG) to take up [3H]choline from the extracellular medium, to synthesize acetylcholine from [3H]choline, and to release [3H]acetylcholine in response to a high K+ concentration, were examined in rats throughout a 24-h cycle. Both the release of [3H]acetylcholine and the synthesis of [3H]acetylcholine from [3H]choline exhibited significant diurnal variations, showing maxima during the first half of the night. After these maxima, nocturnal acetylcholine release and synthesis decayed to daytime levels and remained low until the end of the night. [3H]Choline uptake by rat SCG did not vary significantly throughout a 24-h period. A 1.5-h exposure of rats to darkness at the 5th hour of light phase of the daily photoperiod did not change significantly any parameter studied. A 20-min, 5-Hz, electrical stimulation of the preganglionic trunk of SCG excised from rats at noon increased significantly subsequent K(+)-induced [3H]acetylcholine release but did not change [3H]acetylcholine synthesis. In decentralized SCG of rats subjected to a unilateral SCG decentralization and a contralateral sham-operation 7 days earlier, [3H]acetylcholine release and synthesis were highly reduced or abolished at the decentralized side, while [3H]choline uptake remained unaltered. The present results suggest that an activation of preganglionic rat SCG neurons takes place during the first half of the scotophase.
Gamma aminobutyric acid uptake, release, and effect on36Cl?-influx in bovine pineal gland
Journal of Neural Transmission, Jun 1, 1989
Two apparent affinities for Na+-dependent, 3H-GABA uptake were found in bovine pineal fragments i... more Two apparent affinities for Na+-dependent, 3H-GABA uptake were found in bovine pineal fragments in vitro i.e., a high affinity uptake (Km = 37 +/- 5 microM) and a low affinity uptake (Km = 435 +/- 50 microM). GABA or the neuronal and glial GABA uptake inhibitor nipecotic acid was significantly more effective than the inhibitor of the GABA glial uptake beta-alanine to decrease pineal 3H-GABA uptake. High K+ concentration release 3H-GABA in superfused bovine pineals, no differences in 3H-GABA release among fragments taken from medial, proximal or distal pineal regions being apparent. Superfusion of pineal fragments in the absence of Ca2+ but in the presence of EGTA, Mg2+ or verapamil decreased significantly 3H-GABA release induced by K+. In every case a Ca2+-independent pineal GABA release was found. Preincubation with GABA or nipecotic acid, but not with beta-alanine, blunted subsequent 3H-GABA release. GABA increased 36Cl--influx in pineal homogenates, an effect blocked by picrotoxin. Incubation of pineal homogenates in the presence of aminooxyacetic acid decreased Vmax of glutamic acid decarboxylase, without modifying its Km. These results are compatible with a transmitter or modulator role of GABA in bovine pineal gland.
European Journal of Pharmacology, May 1, 1991
In order to examine whether cyclospo~ne activity in subm~lla~ lymph nodes is dependent on sympath... more In order to examine whether cyclospo~ne activity in subm~lla~ lymph nodes is dependent on sympathetic m~ula~on, rats received a unilateral superior cervical ganglionectomy together with a contralateral sham-operation. Two weeks later, cyclosporine (5 or 20 mg/kg per day s.c.) was injected for five days. Freund's complete adjuvant was injected 1 h before the third injection of cyclosporine and the rats were killed 2 h after the last injection of cyclosporine. A significant increase in omithine decarboxylase activity in submaxillary lymph nodes was observed two weeks after sympathetic denervation. Cyclosporine decreased enzyme activity in submaxillary lymph nodes on the sham-operated side by 67-772 and by 21-41% on the denervated side (P < 0.01). The in~~oration of [ 35S]met~o~e into proteins in ipsilateral subm~lla~ lymph nodes was increased by u~later~ superior cervical ganglionectomy and decreased by cyciosporine to a similar extent in denervated and innervated lymph nodes. Superior cervicaf ganglionectomy decreased by about 93-952 the norepinephrine content of submaxillary lymph nodes regardless of cyclosporine treatment. The results indicate that an appropriate sympathetic neural environment is needed for cyclosporine to have au effect on ornithine decarboxylase activity in lymphoid tissue.
Melatonin reverses pinealectomy-induced decrease of benzodiazepine binding in rat cerebral cortex
Neurochemistry International, 1985
European Journal of Pharmacology, Mar 1, 1994
This study was performed: (1) to assess whether cyclosporine affected the increase in submaxillar... more This study was performed: (1) to assess whether cyclosporine affected the increase in submaxillary lymph node ornithine decarboxylase activity induced by complete Freund's adjuvant injection to rats bearing a regional parasympathetic decentralization; (2) to examine the effect of cyclosporine on cholinergic markers in submaxillary lymph nodes of rats injected with complete Freund's adjuvant or its vehicle. The unilateral parasympathetic decentralization of the submaxillary lymph nodes was achieved by unilateral chorda tympani section; each rat was also contralaterally sham-operated. A 73% decrease of choline acetyltransferase activity and a 78% decrease of neuronal [3H]choline uptake, were found in the ipsilateral side 2 weeks after surgery. Cyclosporine (5 or 20 mg/kg) or its vehicle was s.c. injected once daily for 5 days. Freund's complete adjuvant or its vehicle was injected s.c. 1 h before the 3rd injection of cyclosporine. The animals were killed 2 h after the last cyclosporine injection. Parasympathetic decentralization of the submaxillary lymph nodes was followed, 2 weeks later, by a significant inhibition of cyclosporine activity on Freund's adjuvant-induced ornithine decarboxylase. In rats injected with complete Freund's adjuvant or its vehicle, sympathetic denervation of submaxillary lymph nodes achieved by unilateral superior cervical ganglionectomy, augmented the stimulatory activity of cyclosporine on choline acetyltransferase and neuronal choline uptake. Cyclosporine treatment did not modify the total [3H]choline uptake, regardless of Freund's adjuvant injection or of intactness of the sympathetic innervation. Choline acetyltransferase and choline uptake were significantly augmented by the injection of Freund's adjuvant alone. The results indicate that an appropriate parasympathetic local environment is needed for cyclosporine immunomodulation in lymphoid tissue, and that cyclosporine augmented cholinergic activity in submaxillary lymph nodes, an effect amplified by regional sympathetic denervation. Cholinergic markers in lymphoid tissue increased during the immune reaction.
Serotonin release mechanisms in bovine pineal gland: stimulation by norepinephrine and dopamine
Molecular and Cellular Endocrinology, Jun 1, 1989
An assessment of serotonin (5HT) release was made in bovine pineal gland. Bovine pineal fragments... more An assessment of serotonin (5HT) release was made in bovine pineal gland. Bovine pineal fragments took up [3H]5HT by a Na+-dependent process exhibiting two apparent Km, i.e. a high affinity uptake system (Km = 220 nM) and a low affinity uptake system (Km = 197 microM). A significant release of [3H]5HT was elicited by increasing K+ concentrations in the medium (20-80 mM). Exposure of bovine pineal fragments to varying doses of catecholaminergic agonists indicated that a significant [3H]5HT release was elicited at the following threshold concentrations: 10(-6) M norepinephrine (NE), 10(-7) M dopamine (DA), 10(-6) phenylephrine and 10(-6) M isoproterenol. By employing specific receptor agonists and antagonists, the 5HT release activity of adrenergic agonists was found to be mediated by alpha 1-adrenoceptors, while that of DA by D2-dopaminergic receptors. 5HT release elicited by NE or DA, as well as that by 30 mM K+, was Ca2+-dependent. Both NE and DA increase 45Ca2+ uptake in a dispersed cell preparation of bovine pineal glands. As in the case of 5HT release, the effect of NE and DA on calcium uptake was mediated by alpha 1-adrenoceptors and D2-dopaminergic receptors, respectively. These results indicate that both NE and DA control 5HT release in bovine pineal gland.
Effect of enriched environment housing on glutamate-induced damage in adult rat retina
Investigative Ophthalmology & Visual Science, Jun 16, 2013
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Papers by Ruth Rosenstein