Choroidal Neovascularization Is Inhibited in Splenic-Denervated or Splenectomized Mice with a Concomitant Decrease in Intraocular Macrophage
To determine the involvement of sympathetic activity in choroidal neovascularization (CNV) using laser-induced CNV in a mouse model. We investigated changes in the proportions of intraocular lymphocytes, granulocytes, and three macrophage subtypes (Ly6Chi, Ly6Cint, and Ly6Clo) after laser injury in...
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| Veröffentlicht in: | PloS one 2016-08, Vol.11 (8), p.e0160985-e0160985 |
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| creator | Tan, Xue Fujiu, Katsuhito Manabe, Ichiro Nishida, Junko Yamagishi, Reiko Terashima, Yuya Matsushima, Kouji Kaburaki, Toshikatsu Nagai, Ryozo Yanagi, Yasuo |
| description | To determine the involvement of sympathetic activity in choroidal neovascularization (CNV) using laser-induced CNV in a mouse model.
We investigated changes in the proportions of intraocular lymphocytes, granulocytes, and three macrophage subtypes (Ly6Chi, Ly6Cint, and Ly6Clo) after laser injury in mice using flow cytometry, and evaluated CNV lesion size in mice lacking inflammatory cells. Further, we evaluated the lesion size in mice administered the β3 receptor antagonist, splenic-denervated and splenectomized mice. We also assessed changes in the proportions of intraocular macrophages and peripheral blood monocytes in splenic-denervated and splenectomized mice. Lastly, lesion size was compared between splenic-denervated mice with or without adoptive transfer of macrophages following laser injury. After Ly5.1 mice spleen-derived Ly6Chi cells were transferred into Ly5.2 mice, the proportions of intraocular Ly5.1+Ly6Chi cells were compared.
In WT mice, the proportion of CD4+ T cells recruited into the eye increased progressively from day 3 to day 7 after laser injury, whereas, intraocular CD8+ T cells did not change significantly. Proportions of B220+ cells, granulocytes, and two subtypes of intraocular macrophages (Ly6Chi and Ly6Clo) peaked at day 3 following laser injury. In contrast, Ly6Cint/loCD64+ subtype showed a significantly higher percentage at day 7 after laser injury. There were no differences in lesion size between CD4-/-or Rag2-/-mice and controls, whereas lesion size was significantly reduced in CCR2-/- mice and clodronate liposome-treated mice. CNV lesion area was significantly reduced in mice with β3 blocker treatment, splenic-denervated and splenectomized mice compared with controls. Intraocular Ly6Chi macrophages were also reduced by splenic denervation or splenectomy. Adoptive transfer of spleen-derived Ly6Chi cells increased the lesion size in splenic-denervated mice. Compared with controls, intraocular donor-derived Ly6Chi cells recruited into the eye were reduced in splenic-denervated and splenectomized mice.
Although lymphocytes had little effect on CNV formation, Ly6Chi macrophages/monocytes exacerbated CNV in mice. Sympathetic activity might contribute to CNV via the recruitment of macrophages to the eye. |
| doi_str_mv | 10.1371/journal.pone.0160985 |
| format | Article |
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We investigated changes in the proportions of intraocular lymphocytes, granulocytes, and three macrophage subtypes (Ly6Chi, Ly6Cint, and Ly6Clo) after laser injury in mice using flow cytometry, and evaluated CNV lesion size in mice lacking inflammatory cells. Further, we evaluated the lesion size in mice administered the β3 receptor antagonist, splenic-denervated and splenectomized mice. We also assessed changes in the proportions of intraocular macrophages and peripheral blood monocytes in splenic-denervated and splenectomized mice. Lastly, lesion size was compared between splenic-denervated mice with or without adoptive transfer of macrophages following laser injury. After Ly5.1 mice spleen-derived Ly6Chi cells were transferred into Ly5.2 mice, the proportions of intraocular Ly5.1+Ly6Chi cells were compared.
In WT mice, the proportion of CD4+ T cells recruited into the eye increased progressively from day 3 to day 7 after laser injury, whereas, intraocular CD8+ T cells did not change significantly. Proportions of B220+ cells, granulocytes, and two subtypes of intraocular macrophages (Ly6Chi and Ly6Clo) peaked at day 3 following laser injury. In contrast, Ly6Cint/loCD64+ subtype showed a significantly higher percentage at day 7 after laser injury. There were no differences in lesion size between CD4-/-or Rag2-/-mice and controls, whereas lesion size was significantly reduced in CCR2-/- mice and clodronate liposome-treated mice. CNV lesion area was significantly reduced in mice with β3 blocker treatment, splenic-denervated and splenectomized mice compared with controls. Intraocular Ly6Chi macrophages were also reduced by splenic denervation or splenectomy. Adoptive transfer of spleen-derived Ly6Chi cells increased the lesion size in splenic-denervated mice. Compared with controls, intraocular donor-derived Ly6Chi cells recruited into the eye were reduced in splenic-denervated and splenectomized mice.
Although lymphocytes had little effect on CNV formation, Ly6Chi macrophages/monocytes exacerbated CNV in mice. Sympathetic activity might contribute to CNV via the recruitment of macrophages to the eye.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0160985</identifier><identifier>PMID: 27532664</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adoptive Transfer ; Age ; Angiogenesis ; Animals ; Antigens, Ly - metabolism ; B220 antigen ; Biology and Life Sciences ; Bisphosphonates ; Bone marrow ; CC chemokine receptors ; CCR2 protein ; CD4 antigen ; CD8 antigen ; Cell Movement - immunology ; Chemokines ; Choroidal Neovascularization - immunology ; Choroidal Neovascularization - pathology ; Choroidal Neovascularization - prevention & control ; Clodronic acid ; Comparative analysis ; Cytometry ; Denervation ; Disease Models, Animal ; Engineering and Technology ; Eye ; Eye - immunology ; Eye - pathology ; Eye injuries ; Flow cytometry ; Heart attacks ; Inflammation ; Lasers ; Leukocytes (granulocytic) ; Lymphocytes ; Lymphocytes T ; Macrophages ; Macrophages - classification ; Macrophages - immunology ; Macrophages - pathology ; Macular degeneration ; Male ; Medicine and Health Sciences ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Monocyte chemoattractant protein 1 ; Monocytes ; Mutation ; Neovascularization ; Nervous system ; Peripheral blood ; Physiological aspects ; Preventive medicine ; RAG2 protein ; Receptors, CCR2 - deficiency ; Receptors, CCR2 - genetics ; Recruitment ; Research and Analysis Methods ; Spleen ; Spleen - immunology ; Spleen - innervation ; Spleen - pathology ; Splenectomy ; Studies ; Sympathectomy ; Vascularization</subject><ispartof>PloS one, 2016-08, Vol.11 (8), p.e0160985-e0160985</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Tan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://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>2016 Tan et al 2016 Tan et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c725t-a22dcd82e0aa687d9bc4dd9c9eb1c68f196b3a7ff3011162266deaca27117a853</citedby><cites>FETCH-LOGICAL-c725t-a22dcd82e0aa687d9bc4dd9c9eb1c68f196b3a7ff3011162266deaca27117a853</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/PMC4988653/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4988653/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79472,79473</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27532664$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Abe, Toshiaki</contributor><creatorcontrib>Tan, Xue</creatorcontrib><creatorcontrib>Fujiu, Katsuhito</creatorcontrib><creatorcontrib>Manabe, Ichiro</creatorcontrib><creatorcontrib>Nishida, Junko</creatorcontrib><creatorcontrib>Yamagishi, Reiko</creatorcontrib><creatorcontrib>Terashima, Yuya</creatorcontrib><creatorcontrib>Matsushima, Kouji</creatorcontrib><creatorcontrib>Kaburaki, Toshikatsu</creatorcontrib><creatorcontrib>Nagai, Ryozo</creatorcontrib><creatorcontrib>Yanagi, Yasuo</creatorcontrib><title>Choroidal Neovascularization Is Inhibited in Splenic-Denervated or Splenectomized Mice with a Concomitant Decrease in Intraocular Macrophage</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>To determine the involvement of sympathetic activity in choroidal neovascularization (CNV) using laser-induced CNV in a mouse model.
We investigated changes in the proportions of intraocular lymphocytes, granulocytes, and three macrophage subtypes (Ly6Chi, Ly6Cint, and Ly6Clo) after laser injury in mice using flow cytometry, and evaluated CNV lesion size in mice lacking inflammatory cells. Further, we evaluated the lesion size in mice administered the β3 receptor antagonist, splenic-denervated and splenectomized mice. We also assessed changes in the proportions of intraocular macrophages and peripheral blood monocytes in splenic-denervated and splenectomized mice. Lastly, lesion size was compared between splenic-denervated mice with or without adoptive transfer of macrophages following laser injury. After Ly5.1 mice spleen-derived Ly6Chi cells were transferred into Ly5.2 mice, the proportions of intraocular Ly5.1+Ly6Chi cells were compared.
In WT mice, the proportion of CD4+ T cells recruited into the eye increased progressively from day 3 to day 7 after laser injury, whereas, intraocular CD8+ T cells did not change significantly. Proportions of B220+ cells, granulocytes, and two subtypes of intraocular macrophages (Ly6Chi and Ly6Clo) peaked at day 3 following laser injury. In contrast, Ly6Cint/loCD64+ subtype showed a significantly higher percentage at day 7 after laser injury. There were no differences in lesion size between CD4-/-or Rag2-/-mice and controls, whereas lesion size was significantly reduced in CCR2-/- mice and clodronate liposome-treated mice. CNV lesion area was significantly reduced in mice with β3 blocker treatment, splenic-denervated and splenectomized mice compared with controls. Intraocular Ly6Chi macrophages were also reduced by splenic denervation or splenectomy. Adoptive transfer of spleen-derived Ly6Chi cells increased the lesion size in splenic-denervated mice. Compared with controls, intraocular donor-derived Ly6Chi cells recruited into the eye were reduced in splenic-denervated and splenectomized mice.
Although lymphocytes had little effect on CNV formation, Ly6Chi macrophages/monocytes exacerbated CNV in mice. Sympathetic activity might contribute to CNV via the recruitment of macrophages to the eye.</description><subject>Adoptive Transfer</subject><subject>Age</subject><subject>Angiogenesis</subject><subject>Animals</subject><subject>Antigens, Ly - metabolism</subject><subject>B220 antigen</subject><subject>Biology and Life Sciences</subject><subject>Bisphosphonates</subject><subject>Bone marrow</subject><subject>CC chemokine receptors</subject><subject>CCR2 protein</subject><subject>CD4 antigen</subject><subject>CD8 antigen</subject><subject>Cell Movement - immunology</subject><subject>Chemokines</subject><subject>Choroidal Neovascularization - immunology</subject><subject>Choroidal Neovascularization - pathology</subject><subject>Choroidal Neovascularization - prevention & control</subject><subject>Clodronic acid</subject><subject>Comparative analysis</subject><subject>Cytometry</subject><subject>Denervation</subject><subject>Disease Models, Animal</subject><subject>Engineering and Technology</subject><subject>Eye</subject><subject>Eye - immunology</subject><subject>Eye - pathology</subject><subject>Eye injuries</subject><subject>Flow cytometry</subject><subject>Heart attacks</subject><subject>Inflammation</subject><subject>Lasers</subject><subject>Leukocytes (granulocytic)</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Macrophages</subject><subject>Macrophages - classification</subject><subject>Macrophages - immunology</subject><subject>Macrophages - pathology</subject><subject>Macular degeneration</subject><subject>Male</subject><subject>Medicine and Health Sciences</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Monocyte chemoattractant protein 1</subject><subject>Monocytes</subject><subject>Mutation</subject><subject>Neovascularization</subject><subject>Nervous system</subject><subject>Peripheral blood</subject><subject>Physiological aspects</subject><subject>Preventive medicine</subject><subject>RAG2 protein</subject><subject>Receptors, CCR2 - deficiency</subject><subject>Receptors, CCR2 - genetics</subject><subject>Recruitment</subject><subject>Research and Analysis Methods</subject><subject>Spleen</subject><subject>Spleen - immunology</subject><subject>Spleen - innervation</subject><subject>Spleen - pathology</subject><subject>Splenectomy</subject><subject>Studies</subject><subject>Sympathectomy</subject><subject>Vascularization</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk9tu1DAQhiMEoqXwBggiISG42MWHxHFukKoth5VaKlHg1po4k41X2XixnQJ9Bh4ap7utdlEvKl_E-vPNb894JkmeUzKlvKDvlnZwPXTTte1xSqggpcwfJIe05GwiGOEPd_YHyRPvl4TkXArxODlgRc6ZENlh8nfWWmdNDV36Be0leD104MwVBGP7dO7Ted-aygSsU9OnF-sOe6MnJ9iju4RRtW6jog52Za6icmY0pr9MaFNIZ7bXUQ7Qh_QEtUPwOBrN--DAXp-VnoF2dt3CAp8mjxroPD7bfo-S7x8_fJt9npyef5rPjk8numB5mABjta4lQwIgZFGXlc7qutQlVlQL2dBSVByKpuGEUipYzLRG0MAKSguQOT9KXm581531altIr6ikLM_yktNIzDdEbWGp1s6swP1RFoy6FqxbKHDB6A5VKbJKk4rkGW0yKmogVSw7b3glCZbZ6PV-e9pQrbDWOObe7Znu_-lNqxb2UmWllCLn0eDN1sDZnwP6oFbGa-w66NEO1_fORcklYfdBmZSyIKPrq__QuwuxpRYQczV9Y-MV9WiqjrPYc5mMrRep6R1UXDWujI4N2pio7wW83QuITMDfYQGD92p-8fX-7PmPffb1DtsidKH1thvGbvb7YLYBY-9577C5fQ9K1DhfN9VQ43yp7XzFsBe7b3kbdDNQ_B__myFh</recordid><startdate>20160817</startdate><enddate>20160817</enddate><creator>Tan, Xue</creator><creator>Fujiu, Katsuhito</creator><creator>Manabe, Ichiro</creator><creator>Nishida, Junko</creator><creator>Yamagishi, Reiko</creator><creator>Terashima, Yuya</creator><creator>Matsushima, Kouji</creator><creator>Kaburaki, Toshikatsu</creator><creator>Nagai, Ryozo</creator><creator>Yanagi, Yasuo</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>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20160817</creationdate><title>Choroidal Neovascularization Is Inhibited in Splenic-Denervated or Splenectomized Mice with a Concomitant Decrease in Intraocular Macrophage</title><author>Tan, Xue ; Fujiu, Katsuhito ; Manabe, Ichiro ; Nishida, Junko ; Yamagishi, Reiko ; Terashima, Yuya ; Matsushima, Kouji ; Kaburaki, Toshikatsu ; Nagai, Ryozo ; Yanagi, Yasuo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c725t-a22dcd82e0aa687d9bc4dd9c9eb1c68f196b3a7ff3011162266deaca27117a853</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adoptive Transfer</topic><topic>Age</topic><topic>Angiogenesis</topic><topic>Animals</topic><topic>Antigens, Ly - 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classification</topic><topic>Macrophages - immunology</topic><topic>Macrophages - pathology</topic><topic>Macular degeneration</topic><topic>Male</topic><topic>Medicine and Health Sciences</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Monocyte chemoattractant protein 1</topic><topic>Monocytes</topic><topic>Mutation</topic><topic>Neovascularization</topic><topic>Nervous system</topic><topic>Peripheral blood</topic><topic>Physiological aspects</topic><topic>Preventive medicine</topic><topic>RAG2 protein</topic><topic>Receptors, CCR2 - deficiency</topic><topic>Receptors, CCR2 - genetics</topic><topic>Recruitment</topic><topic>Research and Analysis Methods</topic><topic>Spleen</topic><topic>Spleen - immunology</topic><topic>Spleen - innervation</topic><topic>Spleen - pathology</topic><topic>Splenectomy</topic><topic>Studies</topic><topic>Sympathectomy</topic><topic>Vascularization</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tan, Xue</creatorcontrib><creatorcontrib>Fujiu, Katsuhito</creatorcontrib><creatorcontrib>Manabe, Ichiro</creatorcontrib><creatorcontrib>Nishida, Junko</creatorcontrib><creatorcontrib>Yamagishi, Reiko</creatorcontrib><creatorcontrib>Terashima, Yuya</creatorcontrib><creatorcontrib>Matsushima, Kouji</creatorcontrib><creatorcontrib>Kaburaki, Toshikatsu</creatorcontrib><creatorcontrib>Nagai, Ryozo</creatorcontrib><creatorcontrib>Yanagi, Yasuo</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>ProQuest Nursing and Allied Health Journals</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>ProQuest Health and Medical</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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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tan, Xue</au><au>Fujiu, Katsuhito</au><au>Manabe, Ichiro</au><au>Nishida, Junko</au><au>Yamagishi, Reiko</au><au>Terashima, Yuya</au><au>Matsushima, Kouji</au><au>Kaburaki, Toshikatsu</au><au>Nagai, Ryozo</au><au>Yanagi, Yasuo</au><au>Abe, Toshiaki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Choroidal Neovascularization Is Inhibited in Splenic-Denervated or Splenectomized Mice with a Concomitant Decrease in Intraocular Macrophage</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2016-08-17</date><risdate>2016</risdate><volume>11</volume><issue>8</issue><spage>e0160985</spage><epage>e0160985</epage><pages>e0160985-e0160985</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>To determine the involvement of sympathetic activity in choroidal neovascularization (CNV) using laser-induced CNV in a mouse model.
We investigated changes in the proportions of intraocular lymphocytes, granulocytes, and three macrophage subtypes (Ly6Chi, Ly6Cint, and Ly6Clo) after laser injury in mice using flow cytometry, and evaluated CNV lesion size in mice lacking inflammatory cells. Further, we evaluated the lesion size in mice administered the β3 receptor antagonist, splenic-denervated and splenectomized mice. We also assessed changes in the proportions of intraocular macrophages and peripheral blood monocytes in splenic-denervated and splenectomized mice. Lastly, lesion size was compared between splenic-denervated mice with or without adoptive transfer of macrophages following laser injury. After Ly5.1 mice spleen-derived Ly6Chi cells were transferred into Ly5.2 mice, the proportions of intraocular Ly5.1+Ly6Chi cells were compared.
In WT mice, the proportion of CD4+ T cells recruited into the eye increased progressively from day 3 to day 7 after laser injury, whereas, intraocular CD8+ T cells did not change significantly. Proportions of B220+ cells, granulocytes, and two subtypes of intraocular macrophages (Ly6Chi and Ly6Clo) peaked at day 3 following laser injury. In contrast, Ly6Cint/loCD64+ subtype showed a significantly higher percentage at day 7 after laser injury. There were no differences in lesion size between CD4-/-or Rag2-/-mice and controls, whereas lesion size was significantly reduced in CCR2-/- mice and clodronate liposome-treated mice. CNV lesion area was significantly reduced in mice with β3 blocker treatment, splenic-denervated and splenectomized mice compared with controls. Intraocular Ly6Chi macrophages were also reduced by splenic denervation or splenectomy. Adoptive transfer of spleen-derived Ly6Chi cells increased the lesion size in splenic-denervated mice. Compared with controls, intraocular donor-derived Ly6Chi cells recruited into the eye were reduced in splenic-denervated and splenectomized mice.
Although lymphocytes had little effect on CNV formation, Ly6Chi macrophages/monocytes exacerbated CNV in mice. Sympathetic activity might contribute to CNV via the recruitment of macrophages to the eye.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>27532664</pmid><doi>10.1371/journal.pone.0160985</doi><tpages>e0160985</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2016-08, Vol.11 (8), p.e0160985-e0160985 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1812545931 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS); EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adoptive Transfer Age Angiogenesis Animals Antigens, Ly - metabolism B220 antigen Biology and Life Sciences Bisphosphonates Bone marrow CC chemokine receptors CCR2 protein CD4 antigen CD8 antigen Cell Movement - immunology Chemokines Choroidal Neovascularization - immunology Choroidal Neovascularization - pathology Choroidal Neovascularization - prevention & control Clodronic acid Comparative analysis Cytometry Denervation Disease Models, Animal Engineering and Technology Eye Eye - immunology Eye - pathology Eye injuries Flow cytometry Heart attacks Inflammation Lasers Leukocytes (granulocytic) Lymphocytes Lymphocytes T Macrophages Macrophages - classification Macrophages - immunology Macrophages - pathology Macular degeneration Male Medicine and Health Sciences Mice Mice, Inbred C57BL Mice, Knockout Monocyte chemoattractant protein 1 Monocytes Mutation Neovascularization Nervous system Peripheral blood Physiological aspects Preventive medicine RAG2 protein Receptors, CCR2 - deficiency Receptors, CCR2 - genetics Recruitment Research and Analysis Methods Spleen Spleen - immunology Spleen - innervation Spleen - pathology Splenectomy Studies Sympathectomy Vascularization |
| title | Choroidal Neovascularization Is Inhibited in Splenic-Denervated or Splenectomized Mice with a Concomitant Decrease in Intraocular Macrophage |
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