Differential modulation of retinal degeneration by Ccl2 and Cx3cr1 chemokine signalling
Microglia and macrophages are recruited to sites of retinal degeneration where local cytokines and chemokines determine protective or neurotoxic microglia responses. Defining the role of Ccl2-Ccr2 and Cx3cl1-Cx3cr1 signalling for retinal pathology is of particular interest because of its potential r...
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| Veröffentlicht in: | PloS one 2012-04, Vol.7 (4), p.e35551 |
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| creator | Luhmann, Ulrich F O Lange, Clemens A Robbie, Scott Munro, Peter M G Cowing, Jill A Armer, Hannah E J Luong, Vy Carvalho, Livia S MacLaren, Robert E Fitzke, Frederick W Bainbridge, James W B Ali, Robin R |
| description | Microglia and macrophages are recruited to sites of retinal degeneration where local cytokines and chemokines determine protective or neurotoxic microglia responses. Defining the role of Ccl2-Ccr2 and Cx3cl1-Cx3cr1 signalling for retinal pathology is of particular interest because of its potential role in age-related macular degeneration (AMD). Ccl2, Ccr2, and Cx3cr1 signalling defects impair macrophage trafficking, but have, in several conflicting studies, been reported to show different degrees of age-related retinal degeneration. Ccl2/Cx3cr1 double knockout (CCDKO) mice show an early onset retinal degeneration and have been suggested as a model for AMD. In order to understand phenotypic discrepancies in different chemokine knockout lines and to study how defects in Ccl2 and/or Cx3cr1 signalling contribute to the described early onset retinal degeneration, we defined primary and secondary pathological events in CCDKO mice. To control for genetic background variability, we compared the original phenotype with that of single Ccl2, Cx3cr1 and Ccl2/Cx3cr1 double knockout mice obtained from backcrosses of CCDKO with C57Bl/6 mice. We found that the primary pathological event in CCDKO mice develops in the inferior outer nuclear layer independently of light around postnatal day P14. RPE and vascular lesions develop secondarily with increasing penetrance with age and are clinically similar to retinal telangiectasia not to choroidal neovascularisation. Furthermore, we provide evidence that a third autosomal recessive gene causes the degeneration in CCDKO mice and in all affected re-derived lines and subsequently demonstrated co-segregation of the naturally occurring RD8 mutation in the Crb1 gene. By comparing CCDKO mice with re-derived CCl2(-/-)/Crb1(Rd8/RD8), Cx3cr1(-/-)/Crb1(Rd8/RD8) and CCl2(-/-)/Cx3cr1(-/-)/Crb1(Rd8/RD8) mice, we observed a differential modulation of the retinal phenotype by genetic background and both chemokine signalling pathways. These findings indicate that CCDKO mice are not a model of AMD, but a model for an inherited retinal degeneration that is differentially modulated by Ccl2-Ccr2 and Cx3cl1-Cx3cr1 chemokine signalling. |
| doi_str_mv | 10.1371/journal.pone.0035551 |
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Defining the role of Ccl2-Ccr2 and Cx3cl1-Cx3cr1 signalling for retinal pathology is of particular interest because of its potential role in age-related macular degeneration (AMD). Ccl2, Ccr2, and Cx3cr1 signalling defects impair macrophage trafficking, but have, in several conflicting studies, been reported to show different degrees of age-related retinal degeneration. Ccl2/Cx3cr1 double knockout (CCDKO) mice show an early onset retinal degeneration and have been suggested as a model for AMD. In order to understand phenotypic discrepancies in different chemokine knockout lines and to study how defects in Ccl2 and/or Cx3cr1 signalling contribute to the described early onset retinal degeneration, we defined primary and secondary pathological events in CCDKO mice. To control for genetic background variability, we compared the original phenotype with that of single Ccl2, Cx3cr1 and Ccl2/Cx3cr1 double knockout mice obtained from backcrosses of CCDKO with C57Bl/6 mice. We found that the primary pathological event in CCDKO mice develops in the inferior outer nuclear layer independently of light around postnatal day P14. RPE and vascular lesions develop secondarily with increasing penetrance with age and are clinically similar to retinal telangiectasia not to choroidal neovascularisation. Furthermore, we provide evidence that a third autosomal recessive gene causes the degeneration in CCDKO mice and in all affected re-derived lines and subsequently demonstrated co-segregation of the naturally occurring RD8 mutation in the Crb1 gene. By comparing CCDKO mice with re-derived CCl2(-/-)/Crb1(Rd8/RD8), Cx3cr1(-/-)/Crb1(Rd8/RD8) and CCl2(-/-)/Cx3cr1(-/-)/Crb1(Rd8/RD8) mice, we observed a differential modulation of the retinal phenotype by genetic background and both chemokine signalling pathways. These findings indicate that CCDKO mice are not a model of AMD, but a model for an inherited retinal degeneration that is differentially modulated by Ccl2-Ccr2 and Cx3cl1-Cx3cr1 chemokine signalling.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0035551</identifier><identifier>PMID: 22545116</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Age ; Age related diseases ; Aging ; Animals ; Apoptosis ; Archives & records ; Atherosclerosis ; Autosomal recessive inheritance ; Biology ; Biomedical research ; CCR2 protein ; Chemokine CCL2 - genetics ; Chemokine CCL2 - immunology ; Chemokines ; CRB1 gene ; CX3C Chemokine Receptor 1 ; CX3CR1 protein ; Cytokines ; Defects ; Dendritic cells ; Diabetes ; Diabetic retinopathy ; Female ; Genetics ; Genotype ; House mouse ; Lesions ; Light ; Macrophages ; Macular degeneration ; Male ; Medicine ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Microglia ; Modulation ; Monocyte chemoattractant protein 1 ; Mutation ; Neovascularization ; Nerve Tissue Proteins - genetics ; Nervous system ; Neurotoxicity ; Ophthalmology ; Photoreceptors ; Physiological aspects ; Protein expression ; Proteins ; Receptors, Chemokine - genetics ; Receptors, Chemokine - immunology ; Retina ; Retina - immunology ; Retina - metabolism ; Retina - pathology ; Retinal degeneration ; Retinal Degeneration - genetics ; Retinal Degeneration - immunology ; Retinal Degeneration - pathology ; Science ; Signal transduction ; Signaling</subject><ispartof>PloS one, 2012-04, Vol.7 (4), p.e35551</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Luhmann et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Luhmann et al. 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-7253a1a1c180da0e530a2dd9dece89632d2de33c6b099cd4dc6215f98e29d03</citedby><cites>FETCH-LOGICAL-c692t-7253a1a1c180da0e530a2dd9dece89632d2de33c6b099cd4dc6215f98e29d03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3335860/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3335860/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22545116$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Luhmann, Ulrich F O</creatorcontrib><creatorcontrib>Lange, Clemens A</creatorcontrib><creatorcontrib>Robbie, Scott</creatorcontrib><creatorcontrib>Munro, Peter M G</creatorcontrib><creatorcontrib>Cowing, Jill A</creatorcontrib><creatorcontrib>Armer, Hannah E J</creatorcontrib><creatorcontrib>Luong, Vy</creatorcontrib><creatorcontrib>Carvalho, Livia S</creatorcontrib><creatorcontrib>MacLaren, Robert E</creatorcontrib><creatorcontrib>Fitzke, Frederick W</creatorcontrib><creatorcontrib>Bainbridge, James W B</creatorcontrib><creatorcontrib>Ali, Robin R</creatorcontrib><title>Differential modulation of retinal degeneration by Ccl2 and Cx3cr1 chemokine signalling</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Microglia and macrophages are recruited to sites of retinal degeneration where local cytokines and chemokines determine protective or neurotoxic microglia responses. Defining the role of Ccl2-Ccr2 and Cx3cl1-Cx3cr1 signalling for retinal pathology is of particular interest because of its potential role in age-related macular degeneration (AMD). Ccl2, Ccr2, and Cx3cr1 signalling defects impair macrophage trafficking, but have, in several conflicting studies, been reported to show different degrees of age-related retinal degeneration. Ccl2/Cx3cr1 double knockout (CCDKO) mice show an early onset retinal degeneration and have been suggested as a model for AMD. In order to understand phenotypic discrepancies in different chemokine knockout lines and to study how defects in Ccl2 and/or Cx3cr1 signalling contribute to the described early onset retinal degeneration, we defined primary and secondary pathological events in CCDKO mice. To control for genetic background variability, we compared the original phenotype with that of single Ccl2, Cx3cr1 and Ccl2/Cx3cr1 double knockout mice obtained from backcrosses of CCDKO with C57Bl/6 mice. We found that the primary pathological event in CCDKO mice develops in the inferior outer nuclear layer independently of light around postnatal day P14. RPE and vascular lesions develop secondarily with increasing penetrance with age and are clinically similar to retinal telangiectasia not to choroidal neovascularisation. Furthermore, we provide evidence that a third autosomal recessive gene causes the degeneration in CCDKO mice and in all affected re-derived lines and subsequently demonstrated co-segregation of the naturally occurring RD8 mutation in the Crb1 gene. By comparing CCDKO mice with re-derived CCl2(-/-)/Crb1(Rd8/RD8), Cx3cr1(-/-)/Crb1(Rd8/RD8) and CCl2(-/-)/Cx3cr1(-/-)/Crb1(Rd8/RD8) mice, we observed a differential modulation of the retinal phenotype by genetic background and both chemokine signalling pathways. These findings indicate that CCDKO mice are not a model of AMD, but a model for an inherited retinal degeneration that is differentially modulated by Ccl2-Ccr2 and Cx3cl1-Cx3cr1 chemokine signalling.</description><subject>Age</subject><subject>Age related diseases</subject><subject>Aging</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Archives & records</subject><subject>Atherosclerosis</subject><subject>Autosomal recessive inheritance</subject><subject>Biology</subject><subject>Biomedical research</subject><subject>CCR2 protein</subject><subject>Chemokine CCL2 - genetics</subject><subject>Chemokine CCL2 - immunology</subject><subject>Chemokines</subject><subject>CRB1 gene</subject><subject>CX3C Chemokine Receptor 1</subject><subject>CX3CR1 protein</subject><subject>Cytokines</subject><subject>Defects</subject><subject>Dendritic cells</subject><subject>Diabetes</subject><subject>Diabetic retinopathy</subject><subject>Female</subject><subject>Genetics</subject><subject>Genotype</subject><subject>House mouse</subject><subject>Lesions</subject><subject>Light</subject><subject>Macrophages</subject><subject>Macular degeneration</subject><subject>Male</subject><subject>Medicine</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Microglia</subject><subject>Modulation</subject><subject>Monocyte chemoattractant protein 1</subject><subject>Mutation</subject><subject>Neovascularization</subject><subject>Nerve Tissue Proteins - genetics</subject><subject>Nervous system</subject><subject>Neurotoxicity</subject><subject>Ophthalmology</subject><subject>Photoreceptors</subject><subject>Physiological aspects</subject><subject>Protein expression</subject><subject>Proteins</subject><subject>Receptors, Chemokine - genetics</subject><subject>Receptors, Chemokine - immunology</subject><subject>Retina</subject><subject>Retina - immunology</subject><subject>Retina - metabolism</subject><subject>Retina - pathology</subject><subject>Retinal degeneration</subject><subject>Retinal Degeneration - genetics</subject><subject>Retinal Degeneration - immunology</subject><subject>Retinal Degeneration - pathology</subject><subject>Science</subject><subject>Signal transduction</subject><subject>Signaling</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNkl-L1DAUxYso7rr6DUQLguDDjPnTpM2LsIy6O7Cw4Io-hjS57WRMmzFpZffbm3G6yxQUJA8Nt79zcjmcLHuJ0RLTEr_f-jH0yi13voclQpQxhh9lp1hQsuAE0cdH95PsWYxbhBitOH-anRDCCoYxP82-f7RNAwH6wSqXd96MTg3W97lv8gCDTS_kBlroIRzm9V2-0o7kqjf56pbqgHO9gc7_sD3k0bZJ4GzfPs-eNMpFeDF9z7Kbz5--ri4XV9cX69X51UJzQYZFSRhVWGGNK2QUAkaRIsYIAxoqwSkxxAClmtdICG0KoznBrBEVEGEQPcteH1x3zkc5JRIlpqRgAhFGErE-EMarrdwF26lwJ72y8s_Ah1aqMFjtQNaNLiuhoCiQKDgSVVWqGkpamxoMr8rk9WF6baw7MDqFFpSbmc7_9HYjW_9LUkpZxffrvpkMgv85Qhz-sfJEtSptZfvGJzPd2ajleVGWqOCk3FPLv1DpGOisTp1obJrPBO9mgsQMcDu0aoxRrm--_D97_W3Ovj1iN6DcsInejfu2xDlYHEAdfIwBmofkMJL7St-nIfeVllOlk-zVceoPovsO099GQ_Ey</recordid><startdate>20120424</startdate><enddate>20120424</enddate><creator>Luhmann, Ulrich F O</creator><creator>Lange, Clemens A</creator><creator>Robbie, Scott</creator><creator>Munro, Peter M G</creator><creator>Cowing, Jill A</creator><creator>Armer, Hannah E J</creator><creator>Luong, Vy</creator><creator>Carvalho, Livia S</creator><creator>MacLaren, Robert E</creator><creator>Fitzke, Frederick W</creator><creator>Bainbridge, James W B</creator><creator>Ali, Robin R</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20120424</creationdate><title>Differential modulation of retinal degeneration by Ccl2 and Cx3cr1 chemokine signalling</title><author>Luhmann, Ulrich F O ; Lange, Clemens A ; Robbie, Scott ; Munro, Peter M G ; Cowing, Jill A ; Armer, Hannah E J ; Luong, Vy ; Carvalho, Livia S ; MacLaren, Robert E ; Fitzke, Frederick W ; Bainbridge, James W B ; Ali, Robin R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-7253a1a1c180da0e530a2dd9dece89632d2de33c6b099cd4dc6215f98e29d03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Age</topic><topic>Age related diseases</topic><topic>Aging</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Archives & records</topic><topic>Atherosclerosis</topic><topic>Autosomal recessive inheritance</topic><topic>Biology</topic><topic>Biomedical research</topic><topic>CCR2 protein</topic><topic>Chemokine CCL2 - 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genetics</topic><topic>Receptors, Chemokine - immunology</topic><topic>Retina</topic><topic>Retina - immunology</topic><topic>Retina - metabolism</topic><topic>Retina - pathology</topic><topic>Retinal degeneration</topic><topic>Retinal Degeneration - genetics</topic><topic>Retinal Degeneration - immunology</topic><topic>Retinal Degeneration - pathology</topic><topic>Science</topic><topic>Signal transduction</topic><topic>Signaling</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Luhmann, Ulrich F O</creatorcontrib><creatorcontrib>Lange, Clemens A</creatorcontrib><creatorcontrib>Robbie, Scott</creatorcontrib><creatorcontrib>Munro, Peter M G</creatorcontrib><creatorcontrib>Cowing, Jill A</creatorcontrib><creatorcontrib>Armer, Hannah E J</creatorcontrib><creatorcontrib>Luong, Vy</creatorcontrib><creatorcontrib>Carvalho, Livia S</creatorcontrib><creatorcontrib>MacLaren, Robert E</creatorcontrib><creatorcontrib>Fitzke, Frederick W</creatorcontrib><creatorcontrib>Bainbridge, James W B</creatorcontrib><creatorcontrib>Ali, Robin R</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Defining the role of Ccl2-Ccr2 and Cx3cl1-Cx3cr1 signalling for retinal pathology is of particular interest because of its potential role in age-related macular degeneration (AMD). Ccl2, Ccr2, and Cx3cr1 signalling defects impair macrophage trafficking, but have, in several conflicting studies, been reported to show different degrees of age-related retinal degeneration. Ccl2/Cx3cr1 double knockout (CCDKO) mice show an early onset retinal degeneration and have been suggested as a model for AMD. In order to understand phenotypic discrepancies in different chemokine knockout lines and to study how defects in Ccl2 and/or Cx3cr1 signalling contribute to the described early onset retinal degeneration, we defined primary and secondary pathological events in CCDKO mice. To control for genetic background variability, we compared the original phenotype with that of single Ccl2, Cx3cr1 and Ccl2/Cx3cr1 double knockout mice obtained from backcrosses of CCDKO with C57Bl/6 mice. We found that the primary pathological event in CCDKO mice develops in the inferior outer nuclear layer independently of light around postnatal day P14. RPE and vascular lesions develop secondarily with increasing penetrance with age and are clinically similar to retinal telangiectasia not to choroidal neovascularisation. Furthermore, we provide evidence that a third autosomal recessive gene causes the degeneration in CCDKO mice and in all affected re-derived lines and subsequently demonstrated co-segregation of the naturally occurring RD8 mutation in the Crb1 gene. By comparing CCDKO mice with re-derived CCl2(-/-)/Crb1(Rd8/RD8), Cx3cr1(-/-)/Crb1(Rd8/RD8) and CCl2(-/-)/Cx3cr1(-/-)/Crb1(Rd8/RD8) mice, we observed a differential modulation of the retinal phenotype by genetic background and both chemokine signalling pathways. These findings indicate that CCDKO mice are not a model of AMD, but a model for an inherited retinal degeneration that is differentially modulated by Ccl2-Ccr2 and Cx3cl1-Cx3cr1 chemokine signalling.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22545116</pmid><doi>10.1371/journal.pone.0035551</doi><tpages>e35551</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2012-04, Vol.7 (4), p.e35551 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1324590252 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Age Age related diseases Aging Animals Apoptosis Archives & records Atherosclerosis Autosomal recessive inheritance Biology Biomedical research CCR2 protein Chemokine CCL2 - genetics Chemokine CCL2 - immunology Chemokines CRB1 gene CX3C Chemokine Receptor 1 CX3CR1 protein Cytokines Defects Dendritic cells Diabetes Diabetic retinopathy Female Genetics Genotype House mouse Lesions Light Macrophages Macular degeneration Male Medicine Mice Mice, Inbred C57BL Mice, Knockout Microglia Modulation Monocyte chemoattractant protein 1 Mutation Neovascularization Nerve Tissue Proteins - genetics Nervous system Neurotoxicity Ophthalmology Photoreceptors Physiological aspects Protein expression Proteins Receptors, Chemokine - genetics Receptors, Chemokine - immunology Retina Retina - immunology Retina - metabolism Retina - pathology Retinal degeneration Retinal Degeneration - genetics Retinal Degeneration - immunology Retinal Degeneration - pathology Science Signal transduction Signaling |
| title | Differential modulation of retinal degeneration by Ccl2 and Cx3cr1 chemokine signalling |
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