Synthesis and propagation of complement C3 by microglia/monocytes in the aging retina
Complement activation is thought to contribute to the pathogenesis of age-related macular degeneration (AMD), which may be mediated in part by para-inflammatory processes. We aimed to investigate the expression and localization of C3, a crucial component of the complement system, in the retina durin...
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| description | Complement activation is thought to contribute to the pathogenesis of age-related macular degeneration (AMD), which may be mediated in part by para-inflammatory processes. We aimed to investigate the expression and localization of C3, a crucial component of the complement system, in the retina during the course of aging.
SD rats were born and reared in low-light conditions, and euthanized at post-natal (P) days 100, 450, or 750. Expression of C3, IBA1, and Ccl- and Cxcl- chemokines was assessed by qPCR, and in situ hybridization. Thickness of the ONL was assessed in retinal sections as a measure of photoreceptor loss, and counts were made of C3-expressing monocytes.
C3 expression increased significantly at P750, and correlated with thinning of the ONL, at P750, and up-regulation of GFAP. In situ hybridization showed that C3 was expressed by microglia/monocytes, mainly from within the retinal vasculature, and occasionally the ONL. The number of C3-expressing microglia increased significantly by P750, and coincided spatiotemporally with thinning of the ONL, and up-regulation of Ccl- and Cxcl- chemokines.
Our data suggest that recruited microglia/monocytes contribute to activation of complement in the aging retina, through local expression of C3 mRNA. C3 expression coincides with age-related thinning of the ONL at P750, although it is unclear whether the C3-expressing monocytes are a cause or consequence. These findings provide evidence of activation of complement during natural aging, and may have relevance to cellular events underling the pathogenesis of age-related retinal diseases. |
| doi_str_mv | 10.1371/journal.pone.0093343 |
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SD rats were born and reared in low-light conditions, and euthanized at post-natal (P) days 100, 450, or 750. Expression of C3, IBA1, and Ccl- and Cxcl- chemokines was assessed by qPCR, and in situ hybridization. Thickness of the ONL was assessed in retinal sections as a measure of photoreceptor loss, and counts were made of C3-expressing monocytes.
C3 expression increased significantly at P750, and correlated with thinning of the ONL, at P750, and up-regulation of GFAP. In situ hybridization showed that C3 was expressed by microglia/monocytes, mainly from within the retinal vasculature, and occasionally the ONL. The number of C3-expressing microglia increased significantly by P750, and coincided spatiotemporally with thinning of the ONL, and up-regulation of Ccl- and Cxcl- chemokines.
Our data suggest that recruited microglia/monocytes contribute to activation of complement in the aging retina, through local expression of C3 mRNA. C3 expression coincides with age-related thinning of the ONL at P750, although it is unclear whether the C3-expressing monocytes are a cause or consequence. These findings provide evidence of activation of complement during natural aging, and may have relevance to cellular events underling the pathogenesis of age-related retinal diseases.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0093343</identifier><identifier>PMID: 24705166</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Age ; Age related diseases ; Aging ; Aging (natural) ; Aging - genetics ; Aging - metabolism ; Analysis ; Animals ; Animals, Newborn ; Biology and Life Sciences ; Cell activation ; Chemokines ; Chemokines - genetics ; Chemokines - metabolism ; Complement ; Complement activation ; Complement C3 - genetics ; Complement C3 - metabolism ; Complement component C3 ; Disease ; Gene amplification ; Gene expression ; Glial fibrillary acidic protein ; Glial Fibrillary Acidic Protein - genetics ; Glial Fibrillary Acidic Protein - metabolism ; Health aspects ; Homeostasis ; Immunology ; Inflammation ; Intermediate filament proteins ; Localization ; Macular degeneration ; Medical research ; Medicine and Health Sciences ; Microglia ; Microglia - metabolism ; Monocytes ; Monocytes - metabolism ; mRNA ; Pathogenesis ; Photoreceptors ; Rats ; Rats, Sprague-Dawley ; Research and Analysis Methods ; Retina ; Retina - cytology ; Retina - physiology ; RNA ; Studies ; Thinning</subject><ispartof>PloS one, 2014-04, Vol.9 (4), p.e93343-e93343</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Rutar 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>2014 Rutar et al 2014 Rutar et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-cc53feea8434490bea68c7a629a314729332882a77b8e3ca894393056ef78b553</citedby><cites>FETCH-LOGICAL-c692t-cc53feea8434490bea68c7a629a314729332882a77b8e3ca894393056ef78b553</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/PMC3976274/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3976274/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24705166$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Fletcher, Erica Lucy</contributor><creatorcontrib>Rutar, Matt</creatorcontrib><creatorcontrib>Valter, Krisztina</creatorcontrib><creatorcontrib>Natoli, Riccardo</creatorcontrib><creatorcontrib>Provis, Jan M</creatorcontrib><title>Synthesis and propagation of complement C3 by microglia/monocytes in the aging retina</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Complement activation is thought to contribute to the pathogenesis of age-related macular degeneration (AMD), which may be mediated in part by para-inflammatory processes. We aimed to investigate the expression and localization of C3, a crucial component of the complement system, in the retina during the course of aging.
SD rats were born and reared in low-light conditions, and euthanized at post-natal (P) days 100, 450, or 750. Expression of C3, IBA1, and Ccl- and Cxcl- chemokines was assessed by qPCR, and in situ hybridization. Thickness of the ONL was assessed in retinal sections as a measure of photoreceptor loss, and counts were made of C3-expressing monocytes.
C3 expression increased significantly at P750, and correlated with thinning of the ONL, at P750, and up-regulation of GFAP. In situ hybridization showed that C3 was expressed by microglia/monocytes, mainly from within the retinal vasculature, and occasionally the ONL. The number of C3-expressing microglia increased significantly by P750, and coincided spatiotemporally with thinning of the ONL, and up-regulation of Ccl- and Cxcl- chemokines.
Our data suggest that recruited microglia/monocytes contribute to activation of complement in the aging retina, through local expression of C3 mRNA. C3 expression coincides with age-related thinning of the ONL at P750, although it is unclear whether the C3-expressing monocytes are a cause or consequence. These findings provide evidence of activation of complement during natural aging, and may have relevance to cellular events underling the pathogenesis of age-related retinal diseases.</description><subject>Age</subject><subject>Age related diseases</subject><subject>Aging</subject><subject>Aging (natural)</subject><subject>Aging - genetics</subject><subject>Aging - metabolism</subject><subject>Analysis</subject><subject>Animals</subject><subject>Animals, Newborn</subject><subject>Biology and Life Sciences</subject><subject>Cell activation</subject><subject>Chemokines</subject><subject>Chemokines - genetics</subject><subject>Chemokines - metabolism</subject><subject>Complement</subject><subject>Complement activation</subject><subject>Complement C3 - genetics</subject><subject>Complement C3 - metabolism</subject><subject>Complement component C3</subject><subject>Disease</subject><subject>Gene amplification</subject><subject>Gene expression</subject><subject>Glial fibrillary acidic protein</subject><subject>Glial Fibrillary Acidic Protein - genetics</subject><subject>Glial Fibrillary Acidic Protein - metabolism</subject><subject>Health aspects</subject><subject>Homeostasis</subject><subject>Immunology</subject><subject>Inflammation</subject><subject>Intermediate filament proteins</subject><subject>Localization</subject><subject>Macular degeneration</subject><subject>Medical research</subject><subject>Medicine and Health Sciences</subject><subject>Microglia</subject><subject>Microglia - metabolism</subject><subject>Monocytes</subject><subject>Monocytes - metabolism</subject><subject>mRNA</subject><subject>Pathogenesis</subject><subject>Photoreceptors</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Research and Analysis Methods</subject><subject>Retina</subject><subject>Retina - cytology</subject><subject>Retina - physiology</subject><subject>RNA</subject><subject>Studies</subject><subject>Thinning</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</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>eNqNkk1r3DAQhk1padK0_6C0hkJpD7uxPPqwLoWw9GMhEGiaXsVYlr0KtrSx7NL999V2nbAuORQdJEbPvKMZvUnymmRLAoKc3_qxd9gut96ZZZZJAApPklMiIV_wPIOnR-eT5EUIt1nGoOD8eXKSU5ExwvlpcnO9c8PGBBtSdFW67f0WGxysd6mvU-27bWs644Z0BWm5Szure9-0Fs8777zeDSak1qVRIcXGuibtzWAdvkye1dgG82raz5KbL59_rL4tLq--rlcXlwvNZT4stGZQG4MFBUplVhrkhRbIc4lAqMhjT3lR5ChEWRjQWEgKEjLGTS2KkjE4S94edLetD2qaSFBECiGokJJEYn0gKo-3atvbDvud8mjV34DvG4X9YHVrFOFVSbisippJqgUpeS1BcgBG67qoyqj1aao2lp2pdBxLj-1MdH7j7EY1_pcCKXguaBT4MAn0_m40YVCdDdq0LTrjx_huRigFdkDf_YM-3t1ENRgbsK72sa7ei6oLEIwVuQARqeUjVFyVif8Z7VPbGJ8lfJwlRGYwv4cGxxDU-vr7_7NXP-fs-yN2Y7AdNsG3495uYQ7SAxjdFkJv6ochk0zt3X8_DbV3v5rcH9PeHH_QQ9K93eEPt17-Qw</recordid><startdate>20140401</startdate><enddate>20140401</enddate><creator>Rutar, Matt</creator><creator>Valter, Krisztina</creator><creator>Natoli, Riccardo</creator><creator>Provis, Jan M</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>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>20140401</creationdate><title>Synthesis and propagation of complement C3 by microglia/monocytes in the aging retina</title><author>Rutar, Matt ; Valter, Krisztina ; Natoli, Riccardo ; Provis, Jan M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-cc53feea8434490bea68c7a629a314729332882a77b8e3ca894393056ef78b553</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Age</topic><topic>Age related diseases</topic><topic>Aging</topic><topic>Aging (natural)</topic><topic>Aging - genetics</topic><topic>Aging - metabolism</topic><topic>Analysis</topic><topic>Animals</topic><topic>Animals, Newborn</topic><topic>Biology and Life Sciences</topic><topic>Cell activation</topic><topic>Chemokines</topic><topic>Chemokines - genetics</topic><topic>Chemokines - metabolism</topic><topic>Complement</topic><topic>Complement activation</topic><topic>Complement C3 - genetics</topic><topic>Complement C3 - metabolism</topic><topic>Complement component C3</topic><topic>Disease</topic><topic>Gene amplification</topic><topic>Gene expression</topic><topic>Glial fibrillary acidic protein</topic><topic>Glial Fibrillary Acidic Protein - genetics</topic><topic>Glial Fibrillary Acidic Protein - metabolism</topic><topic>Health aspects</topic><topic>Homeostasis</topic><topic>Immunology</topic><topic>Inflammation</topic><topic>Intermediate filament proteins</topic><topic>Localization</topic><topic>Macular degeneration</topic><topic>Medical research</topic><topic>Medicine and Health Sciences</topic><topic>Microglia</topic><topic>Microglia - 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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>Rutar, Matt</au><au>Valter, Krisztina</au><au>Natoli, Riccardo</au><au>Provis, Jan M</au><au>Fletcher, Erica Lucy</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis and propagation of complement C3 by microglia/monocytes in the aging retina</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-04-01</date><risdate>2014</risdate><volume>9</volume><issue>4</issue><spage>e93343</spage><epage>e93343</epage><pages>e93343-e93343</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Complement activation is thought to contribute to the pathogenesis of age-related macular degeneration (AMD), which may be mediated in part by para-inflammatory processes. We aimed to investigate the expression and localization of C3, a crucial component of the complement system, in the retina during the course of aging.
SD rats were born and reared in low-light conditions, and euthanized at post-natal (P) days 100, 450, or 750. Expression of C3, IBA1, and Ccl- and Cxcl- chemokines was assessed by qPCR, and in situ hybridization. Thickness of the ONL was assessed in retinal sections as a measure of photoreceptor loss, and counts were made of C3-expressing monocytes.
C3 expression increased significantly at P750, and correlated with thinning of the ONL, at P750, and up-regulation of GFAP. In situ hybridization showed that C3 was expressed by microglia/monocytes, mainly from within the retinal vasculature, and occasionally the ONL. The number of C3-expressing microglia increased significantly by P750, and coincided spatiotemporally with thinning of the ONL, and up-regulation of Ccl- and Cxcl- chemokines.
Our data suggest that recruited microglia/monocytes contribute to activation of complement in the aging retina, through local expression of C3 mRNA. C3 expression coincides with age-related thinning of the ONL at P750, although it is unclear whether the C3-expressing monocytes are a cause or consequence. These findings provide evidence of activation of complement during natural aging, and may have relevance to cellular events underling the pathogenesis of age-related retinal diseases.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24705166</pmid><doi>10.1371/journal.pone.0093343</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Age Age related diseases Aging Aging (natural) Aging - genetics Aging - metabolism Analysis Animals Animals, Newborn Biology and Life Sciences Cell activation Chemokines Chemokines - genetics Chemokines - metabolism Complement Complement activation Complement C3 - genetics Complement C3 - metabolism Complement component C3 Disease Gene amplification Gene expression Glial fibrillary acidic protein Glial Fibrillary Acidic Protein - genetics Glial Fibrillary Acidic Protein - metabolism Health aspects Homeostasis Immunology Inflammation Intermediate filament proteins Localization Macular degeneration Medical research Medicine and Health Sciences Microglia Microglia - metabolism Monocytes Monocytes - metabolism mRNA Pathogenesis Photoreceptors Rats Rats, Sprague-Dawley Research and Analysis Methods Retina Retina - cytology Retina - physiology RNA Studies Thinning |
| title | Synthesis and propagation of complement C3 by microglia/monocytes in the aging retina |
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