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      Cyclic GMP in the pig vitreous and retina after experimental retinal detachment

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          Abstract

          Purpose

          Earlier studies have revealed a decreased level of cGMP in vitreous fluid obtained from patients with a retinal detachment. To further investigate this phenomenon, we developed an experimental retinal detachment model in pigs.

          Methods

          Experimental unilateral retinal detachments were induced in pig eyes by subretinal injection of 0.25% sodium hyaluronate. Fourteen days later the vitreous and retinas were analyzed for cGMP expression. Following enucleation, the retinas were incubated in the presence of a nonselective phosphodiesterase inhibitor (IBMX), and the particulate guanylyl cyclase stimulator atrial natriuretic peptide (ANP) or the soluble guanylyl cyclase stimulator sodium nitroprusside (SNP). cGMP was visualized in retinal wholemounts by immunochemistry combined with a computer based stereology system. cGMP levels in vitreous were determined by ELISA.

          Results

          The mean vitreous cGMP level in pig eyes with a retinal detachment (1.45 pmol/ml) was significantly lower compared to the mean level of cGMP in healthy pig eyes (4.61 pmol/ml; p=0.028 was considered significant). In the inner retina, ANP as well as SNP induced cGMP immunoreactivity in both detached and healthy retinas. After incubation with ANP, cGMP could also be detected in the outer nuclear layer of the detached retina, whereas this was not the case in the normal retina.

          Conclusions

          Experimental retinal detachment in the pig eye leads to a decrease of cGMP levels in vitreous similar to that observed in clinical studies. This model may be helpful to analyze the mechanisms involved in cGMP dynamics following retinal detachment.

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          Most cited references26

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          Cyclic nucleotide phosphodiesterases: functional implications of multiple isoforms.

          J Beavo (1995)
          In the last few years there has been a veritable explosion of knowledge about cyclic nucleotide phosphodiesterases. In particular, the accumulating data showing that there are a large number of different phosphodiesterase isozymes have triggered an equally large increase in interest about these enzymes. At least seven different gene families of cyclic nucleotide phosphodiesterase are currently known to exist in mammalian tissues. Most families contain several distinct genes, and many of these genes are expressed in different tissues as functionally unique alternative splice variants. This article reviews many of the more important aspects about the structure, cellular localization, and regulation of each family of phosphodiesterases. Particular emphasis is placed on new information obtained in the last few years about how differential expression and regulation of individual phosphodiesterase isozymes relate to their function(s) in the body. A substantial discussion of the currently accepted nomenclature is also included. Finally, a brief discussion is included about how the differences among distinct phosphodiesterase isozymes are beginning to be used as the basis for developing therapeutic agents.
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            Differential properties of two gap junctional pathways made by AII amacrine cells.

            The retina is sensitive to light stimuli varying over more than 12 log units in intensity. It accomplishes this, in part, by switching between rod-dominated circuits designed for maximum utilization of scarce photons and cone circuits designed for greater acuity. Rod signals are integrated into the cone pathways through AII amacrine cells, which are connected by gap junctions both to other AII amacrine cells and to cone bipolar cells. To determine the relative permeabilities of the two junctional pathways, we have measured the distribution of biotinylated tracers across this heterologous cell assembly after injecting a single AII amacrine cell. We found that neurobiotin (relative molecular mass, 286) passed easily through both types of gap junctions, but that biotin-X cadaverine (relative molecular mass, 442) passed through AII/bipolar cell gap junctions poorly compared to AII/AII gap junctions. Thus, the AII/bipolar cell channel has a lower permeability to large molecules than does the AII/AII amacrine cell channel. The two pathways are also regulated differently. Dopamine and cyclic AMP agonists, known to diminish AII-AII coupling, did not change the relative labelling intensity of AII to bipolar cells. However, nitric oxide and cGMP agonists selectively reduced labelling in bipolar cells relative to AII amacrine cells, perhaps by acting at the bipolar side of this gap junction. This suggests that increased cGMP controls the network switching between rod and cone pathways associated with light adaptation.
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              Capturing cyclic nucleotides in action: snapshots from crystallographic studies.

              Fifty years ago, cyclic AMP was discovered as a second messenger of hormone action, heralding the age of signal transduction. Many cellular processes were found to be regulated by cAMP and the related cyclic GMP. Cyclic nucleotides function by binding to and activating their effectors - protein kinase A, protein kinase G, cyclic-nucleotide-regulated ion channels and the guanine nucleotide-exchange factor Epac. Recent structural insights have now made it possible to propose a general structural mechanism for how cyclic nucleotides regulate these proteins.
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                Author and article information

                Journal
                Mol Vis
                MV
                Molecular Vision
                Molecular Vision
                1090-0535
                2008
                04 February 2008
                : 14
                : 255-261
                Affiliations
                [1 ]Eye Research Institute Maastricht, Department of Ophthalmology, University Hospital Maastricht, The Netherlands
                [2 ]European Graduate School of Neuroscience (EURON), Psychiatry and Neuropsychology, University of Maastricht, The Netherlands
                [3 ]Animal Sciences Group, Wageningen UR, Lelystad, The Netherlands
                Author notes
                Corresponding author: Aize Kijlstra, Department of Ophthalmology, University Hospital Maastricht, P.O. Box 5800, P. Debyelaan 25, 6202 AZ, Maastricht, The Netherlands; Phone: 0031-43-3875646; FAX: 0031-43-3875343; email: aize.kijlstra@wur.nl
                Article
                31 2007MOLVIS0246
                2254957
                18334939
                b37adf96-95e1-40ef-81c1-f836376912b7
                Copyright © 2008 Molecular Vision.

                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 work is properly cited.

                History
                : 16 April 2007
                : 23 January 2008
                Categories
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                Vision sciences
                Vision sciences

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