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      Influence of the Hypothalamic Arcuate Nucleus on Intraocular Pressure and the Role of Opioid Peptides

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      PLoS ONE
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          Abstract

          Background

          An opioid peptide neuron/humoral feedback regulation might be involved in changes of intraocular pressure (IOP). The aims of this study are to investigate the effects of arcuate nucleus (ARC) and opioid peptides on intraocular pressure (IOP).

          Methods

          Fifty-four healthy purebred New Zealand white rabbits (108eyes) were randomly divided into 4 groups, including control group, electrical stimulation group, [D-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO) group, and [D-Pen 2, D-Pen5]- enkephalin (DPDPE) group. Bilateral IOP was measured after unilateral electrical stimulation of the ARC or unilateral microinjection into the ARC of the selective μ-opioid receptor agonist DAMGO or the selective δ opioid receptor agonist DPDPE, both alone and after pre-administration of either the non-selective opioid receptor antagonist naloxone or saline.

          Results

          Both electrical stimulation in ARC and micro-injection either <mu> or <delta> opioid receptor agonists, DAMGO or DPDPE, respectively, caused a significant bilateral reduction in IOP (P<0.05) which was more pronounced in the ipsilateral than in the contralateral eye. Pretreatment with naloxone prevented some, but not all IOP reductions.

          Conclusion

          The ARC takes part in the negative regulation of IOP, an action that may involve opioid neurons.

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          Most cited references21

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          Selectivity and Specificity of Sphingosine-1-Phosphate Receptor Ligands: Caveats and Critical Thinking in Characterizing Receptor-Mediated Effects

          Receptors for sphingosine-1-phosphate (S1P) have been identified only recently. Their medicinal chemistry is therefore still in its infancy, and few selective agonists or antagonists are available. Furthermore, the selectivity of S1P receptor agonists or antagonists is not well established. JTE-013 and BML-241 (also known as CAY10444), used extensively as specific S1P2 and S1P3 receptors antagonists respectively, are cases in point. When analyzing S1P-induced vasoconstriction in mouse basilar artery, we observed that JTE-013 inhibited not only the effect of S1P, but also the effect of U46619, endothelin-1 or high KCl; JTE-013 strongly inhibited responses to S1P in S1P2 receptor knockout mice. Similarly, BML-241 has been shown to inhibit increases in intracellular Ca2+ concentration via P2 receptor or α1A-adrenoceptor stimulation and α1A-adrenoceptor-mediated contraction of rat mesenteric artery, while it did not affect S1P3-mediated decrease of forskolin-induced cyclic AMP accumulation. Another putative S1P1/3 receptor antagonist, VPC23019, does not inhibit S1P3-mediated vasoconstriction. With these examples in mind, we discuss caveats about relying on available pharmacological tools to characterize receptor subtypes.
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            Dopamine-₃ receptor modulates intraocular pressure: implications for glaucoma.

            The aim of the present study was to investigate the role of D₃ receptor on intraocular pressure regulation using WT and KO D₃R⁻/⁻ mice. Both mice were used with normal eye pressure or steroid-induced ocular hypertension. As measured by tonometry, the topical application of 7-OH-DPAT, a dopamine D₃-preferring receptor agonist, significantly decreased, in a dose-dependent manner, the intraocular pressure in WT mice both in an ocular normotensive group and an ocular hypertensive group. Pretreatment with U-99194A, a D₃ receptor antagonist, reverted 7-OH-DPAT induced ocular hypotension in WT mice. No change of intraocular pressure was observed after topical application of 7-OH-DPAT in KO D₃R⁻/⁻ mice. PCR analysis demonstrated the presence of all dopamine receptor genes in eye tissues obtained from WT mice, and the lack of D₃R mRNAs in KO mice. The present study identified the D₃R subtype as the most important receptor of the dopaminergic system to modulate intraocular pressure with relevant implications for glaucoma that represents one of the most crippling optic neuropathies. Copyright © 2011 Elsevier Inc. All rights reserved.
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              Ocular hypotension induced by electroacupuncture.

              The purpose of this study was to investigate the effects of electroacupuncture (EA) on aqueous humor dynamics in rabbits. EA stimulation was performed through two acupuncture needles placed in close proximity to the sciatic nerve. The sites of needle entry were anesthetized. After 1 hr of EA stimulation, intraocular pressure (IOP) decreased and was accompanied by reductions of blood pressure and aqueous humor flow rate. The maximum reduction of IOP was 9 mmHg at 3 hr and decreases in norepinephrine and dopamine levels in aqueous humor occurred simultaneously. In addition, EA stimulation induced an 8-fold increase of endorphin levels in aqueous humor. Ocular hypotension induced by EA lasted for more than 9 hrs and was antagonized by naloxone pretreatment. Furthermore, the EA-induced ocular hypotension was reduced markedly in sympathetically denervated eyes compared with the response of intact, normal eyes. Antagonism of EA-induced ocular hypotension by naloxone, suppression of aqueous humor flow and catecholamine levels by EA and elevation of endorphin levels in aqueous humor by EA indicate that opioids/opiate receptors are involved in modulating ocular hydrodynamics in response to EA.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2014
                1 April 2014
                : 9
                : 4
                : e82315
                Affiliations
                [1 ]Department of Ophthalmology, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China
                [2 ]Department of Ophthalmology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
                Univeristy of Melbourne, Australia
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: ZY. Performed the experiments: JJ GX. Analyzed the data: JJ. Contributed reagents/materials/analysis tools: JJ GX ZY. Wrote the paper: JJ. Guarantor of integrity of the entire study: ZY. Literature research: GX. Clinical studies: GX.

                Article
                PONE-D-13-14768
                10.1371/journal.pone.0082315
                3972173
                24691128
                f302b034-220b-4bf4-a2bd-0f9b105b8baa
                Copyright @ 2014

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 9 April 2013
                : 22 October 2013
                Page count
                Pages: 8
                Funding
                No current external funding sources for this study.
                Categories
                Research Article
                Biology
                Model Organisms
                Animal Models
                Molecular Cell Biology
                Signal Transduction
                Mechanisms of Signal Transduction
                Feedback Regulation
                Neuroscience
                Neurochemistry
                Neurochemicals
                Neuropeptides
                Mathematics
                Statistics
                Biostatistics
                Medicine
                Ophthalmology
                Glaucoma
                Surgery
                Ophthalmology

                Uncategorized
                Uncategorized

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