α-Crystallin protects RGC survival and inhibits microglial activation after optic nerve crush
Activation of retinal microglial cells (RMCs) is known to contribute to retinal ganglion cell (RGC) death after optic nerve injury. The purpose of this study was to investigate the effects of intravenous injection of α-crystallin on RGC survival and RMC activation in a rat model of optic nerve crush...
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| Veröffentlicht in: | Life sciences (1973) 2014-01, Vol.94 (1), p.17-23 |
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| creator | Wu, Nan Yu, Jia Chen, Shaojun Xu, Jiangning Ying, Xi Ye, Mao Li, Yiru Wang, Yi |
| description | Activation of retinal microglial cells (RMCs) is known to contribute to retinal ganglion cell (RGC) death after optic nerve injury. The purpose of this study was to investigate the effects of intravenous injection of α-crystallin on RGC survival and RMC activation in a rat model of optic nerve crush.
RGCs were retrogradely labeled with fluorogold. Rats were intravenously injected with normal saline or α-crystallin (0.05g/kg, 0.5g/kg, and 5g/kg) at 2, 4, 6, 8, 10, and 12days after the optic nerve crush. Activated RMCs were characterized using immunofluorescence labeling with CD11b, and TNF-α and iNOS expression was detected using immunoblot analyses. We analyzed the morphology and numbers of RGC and RMC 2 and 4weeks after injury using fluorescence and confocal microscopy.
The number of RGCs decreased after optic nerve injury, accompanied by significantly increased numbers of activated RMCs. Intravenous injection of α-crystallin decreased the number of RMCs, and enhanced the number of RGCs compared to saline injection. α-Crystallin administration inhibited TNF-α and iNOS protein expression induced by optic nerve injury.
Our results suggest that α-crystallin promotes RGC survival and inhibits RMC activation. Intravenous injection of α-crystallin could be a possible strategy for the treatment of optic nerve injury. |
| doi_str_mv | 10.1016/j.lfs.2013.10.034 |
| format | Article |
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RGCs were retrogradely labeled with fluorogold. Rats were intravenously injected with normal saline or α-crystallin (0.05g/kg, 0.5g/kg, and 5g/kg) at 2, 4, 6, 8, 10, and 12days after the optic nerve crush. Activated RMCs were characterized using immunofluorescence labeling with CD11b, and TNF-α and iNOS expression was detected using immunoblot analyses. We analyzed the morphology and numbers of RGC and RMC 2 and 4weeks after injury using fluorescence and confocal microscopy.
The number of RGCs decreased after optic nerve injury, accompanied by significantly increased numbers of activated RMCs. Intravenous injection of α-crystallin decreased the number of RMCs, and enhanced the number of RGCs compared to saline injection. α-Crystallin administration inhibited TNF-α and iNOS protein expression induced by optic nerve injury.
Our results suggest that α-crystallin promotes RGC survival and inhibits RMC activation. Intravenous injection of α-crystallin could be a possible strategy for the treatment of optic nerve injury.</description><identifier>ISSN: 0024-3205</identifier><identifier>EISSN: 1879-0631</identifier><identifier>DOI: 10.1016/j.lfs.2013.10.034</identifier><identifier>PMID: 24220677</identifier><language>eng</language><publisher>Netherlands: Elsevier Inc</publisher><subject>alpha-Crystallins - administration & dosage ; alpha-Crystallins - pharmacology ; Animals ; Blotting, Western ; Cell Survival - drug effects ; Crystallin ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Female ; Fluorescent Antibody Technique ; Injections, Intravenous ; Male ; Microglia - drug effects ; Microglia - metabolism ; Microscopy, Confocal ; Microscopy, Fluorescence ; Nerve Crush ; Nitric Oxide Synthase Type II - genetics ; Optic Nerve Injuries - drug therapy ; Optic Nerve Injuries - pathology ; Optic nerve injury ; Rats ; Rats, Long-Evans ; Retinal ganglion cell ; Retinal Ganglion Cells - drug effects ; Retinal Ganglion Cells - metabolism ; Retinal microglial activation ; Time Factors ; Tumor Necrosis Factor-alpha - genetics</subject><ispartof>Life sciences (1973), 2014-01, Vol.94 (1), p.17-23</ispartof><rights>2014 Elsevier Inc.</rights><rights>Copyright © 2014 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c386t-6535da21c06a48a2b26f2c28cc71416850293ce8c10589fa54259690a97fb4d83</citedby><cites>FETCH-LOGICAL-c386t-6535da21c06a48a2b26f2c28cc71416850293ce8c10589fa54259690a97fb4d83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.lfs.2013.10.034$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24220677$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wu, Nan</creatorcontrib><creatorcontrib>Yu, Jia</creatorcontrib><creatorcontrib>Chen, Shaojun</creatorcontrib><creatorcontrib>Xu, Jiangning</creatorcontrib><creatorcontrib>Ying, Xi</creatorcontrib><creatorcontrib>Ye, Mao</creatorcontrib><creatorcontrib>Li, Yiru</creatorcontrib><creatorcontrib>Wang, Yi</creatorcontrib><title>α-Crystallin protects RGC survival and inhibits microglial activation after optic nerve crush</title><title>Life sciences (1973)</title><addtitle>Life Sci</addtitle><description>Activation of retinal microglial cells (RMCs) is known to contribute to retinal ganglion cell (RGC) death after optic nerve injury. The purpose of this study was to investigate the effects of intravenous injection of α-crystallin on RGC survival and RMC activation in a rat model of optic nerve crush.
RGCs were retrogradely labeled with fluorogold. Rats were intravenously injected with normal saline or α-crystallin (0.05g/kg, 0.5g/kg, and 5g/kg) at 2, 4, 6, 8, 10, and 12days after the optic nerve crush. Activated RMCs were characterized using immunofluorescence labeling with CD11b, and TNF-α and iNOS expression was detected using immunoblot analyses. We analyzed the morphology and numbers of RGC and RMC 2 and 4weeks after injury using fluorescence and confocal microscopy.
The number of RGCs decreased after optic nerve injury, accompanied by significantly increased numbers of activated RMCs. Intravenous injection of α-crystallin decreased the number of RMCs, and enhanced the number of RGCs compared to saline injection. α-Crystallin administration inhibited TNF-α and iNOS protein expression induced by optic nerve injury.
Our results suggest that α-crystallin promotes RGC survival and inhibits RMC activation. Intravenous injection of α-crystallin could be a possible strategy for the treatment of optic nerve injury.</description><subject>alpha-Crystallins - administration & dosage</subject><subject>alpha-Crystallins - pharmacology</subject><subject>Animals</subject><subject>Blotting, Western</subject><subject>Cell Survival - drug effects</subject><subject>Crystallin</subject><subject>Disease Models, Animal</subject><subject>Dose-Response Relationship, Drug</subject><subject>Female</subject><subject>Fluorescent Antibody Technique</subject><subject>Injections, Intravenous</subject><subject>Male</subject><subject>Microglia - drug effects</subject><subject>Microglia - metabolism</subject><subject>Microscopy, Confocal</subject><subject>Microscopy, Fluorescence</subject><subject>Nerve Crush</subject><subject>Nitric Oxide Synthase Type II - genetics</subject><subject>Optic Nerve Injuries - drug therapy</subject><subject>Optic Nerve Injuries - pathology</subject><subject>Optic nerve injury</subject><subject>Rats</subject><subject>Rats, Long-Evans</subject><subject>Retinal ganglion cell</subject><subject>Retinal Ganglion Cells - drug effects</subject><subject>Retinal Ganglion Cells - metabolism</subject><subject>Retinal microglial activation</subject><subject>Time Factors</subject><subject>Tumor Necrosis Factor-alpha - genetics</subject><issn>0024-3205</issn><issn>1879-0631</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkdtKAzEQhoMoth4ewBvJpTdbJ8fN4pUUTyAIoreGNJu1KdvdmmQLPpYv4jOZUvVSr4aZ-eaH-X-ETghMCBB5vpi0TZxQICz3E2B8B42JKqsCJCO7aAxAecEoiBE6iHEBAEKUbB-NKKcUZFmO0cvnRzEN7zGZtvUdXoU-OZsifryZ4jiEtV-bFpuuxr6b-5nPm6W3oX9t_WZuU94n33fYNMkF3K-St7hzYe2wDUOcH6G9xrTRHX_XQ_R8ffU0vS3uH27uppf3hWVKpkIKJmpDiQVpuDJ0RmVDLVXWloQTqQTQilmnLAGhqsYITkUlKzBV2cx4rdghOtvq5gfeBheTXvpoXduazvVD1ERwDqSsGPkf5RWUgirOMkq2aP44xuAavQp-acK7JqA3CeiFzgnoTQKbUU4g35x-yw-zpat_L34sz8DFFnDZj7V3QUfrXWdd7UO2Xte9_0P-C3GclpA</recordid><startdate>20140114</startdate><enddate>20140114</enddate><creator>Wu, Nan</creator><creator>Yu, Jia</creator><creator>Chen, Shaojun</creator><creator>Xu, Jiangning</creator><creator>Ying, Xi</creator><creator>Ye, Mao</creator><creator>Li, Yiru</creator><creator>Wang, Yi</creator><general>Elsevier Inc</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>7X8</scope><scope>7TK</scope></search><sort><creationdate>20140114</creationdate><title>α-Crystallin protects RGC survival and inhibits microglial activation after optic nerve crush</title><author>Wu, Nan ; Yu, Jia ; Chen, Shaojun ; Xu, Jiangning ; Ying, Xi ; Ye, Mao ; Li, Yiru ; Wang, Yi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c386t-6535da21c06a48a2b26f2c28cc71416850293ce8c10589fa54259690a97fb4d83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>alpha-Crystallins - administration & dosage</topic><topic>alpha-Crystallins - pharmacology</topic><topic>Animals</topic><topic>Blotting, Western</topic><topic>Cell Survival - drug effects</topic><topic>Crystallin</topic><topic>Disease Models, Animal</topic><topic>Dose-Response Relationship, Drug</topic><topic>Female</topic><topic>Fluorescent Antibody Technique</topic><topic>Injections, Intravenous</topic><topic>Male</topic><topic>Microglia - drug effects</topic><topic>Microglia - metabolism</topic><topic>Microscopy, Confocal</topic><topic>Microscopy, Fluorescence</topic><topic>Nerve Crush</topic><topic>Nitric Oxide Synthase Type II - genetics</topic><topic>Optic Nerve Injuries - drug therapy</topic><topic>Optic Nerve Injuries - pathology</topic><topic>Optic nerve injury</topic><topic>Rats</topic><topic>Rats, Long-Evans</topic><topic>Retinal ganglion cell</topic><topic>Retinal Ganglion Cells - drug effects</topic><topic>Retinal Ganglion Cells - metabolism</topic><topic>Retinal microglial activation</topic><topic>Time Factors</topic><topic>Tumor Necrosis Factor-alpha - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wu, Nan</creatorcontrib><creatorcontrib>Yu, Jia</creatorcontrib><creatorcontrib>Chen, Shaojun</creatorcontrib><creatorcontrib>Xu, Jiangning</creatorcontrib><creatorcontrib>Ying, Xi</creatorcontrib><creatorcontrib>Ye, Mao</creatorcontrib><creatorcontrib>Li, Yiru</creatorcontrib><creatorcontrib>Wang, Yi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Neurosciences Abstracts</collection><jtitle>Life sciences (1973)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wu, Nan</au><au>Yu, Jia</au><au>Chen, Shaojun</au><au>Xu, Jiangning</au><au>Ying, Xi</au><au>Ye, Mao</au><au>Li, Yiru</au><au>Wang, Yi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>α-Crystallin protects RGC survival and inhibits microglial activation after optic nerve crush</atitle><jtitle>Life sciences (1973)</jtitle><addtitle>Life Sci</addtitle><date>2014-01-14</date><risdate>2014</risdate><volume>94</volume><issue>1</issue><spage>17</spage><epage>23</epage><pages>17-23</pages><issn>0024-3205</issn><eissn>1879-0631</eissn><abstract>Activation of retinal microglial cells (RMCs) is known to contribute to retinal ganglion cell (RGC) death after optic nerve injury. The purpose of this study was to investigate the effects of intravenous injection of α-crystallin on RGC survival and RMC activation in a rat model of optic nerve crush.
RGCs were retrogradely labeled with fluorogold. Rats were intravenously injected with normal saline or α-crystallin (0.05g/kg, 0.5g/kg, and 5g/kg) at 2, 4, 6, 8, 10, and 12days after the optic nerve crush. Activated RMCs were characterized using immunofluorescence labeling with CD11b, and TNF-α and iNOS expression was detected using immunoblot analyses. We analyzed the morphology and numbers of RGC and RMC 2 and 4weeks after injury using fluorescence and confocal microscopy.
The number of RGCs decreased after optic nerve injury, accompanied by significantly increased numbers of activated RMCs. Intravenous injection of α-crystallin decreased the number of RMCs, and enhanced the number of RGCs compared to saline injection. α-Crystallin administration inhibited TNF-α and iNOS protein expression induced by optic nerve injury.
Our results suggest that α-crystallin promotes RGC survival and inhibits RMC activation. Intravenous injection of α-crystallin could be a possible strategy for the treatment of optic nerve injury.</abstract><cop>Netherlands</cop><pub>Elsevier Inc</pub><pmid>24220677</pmid><doi>10.1016/j.lfs.2013.10.034</doi><tpages>7</tpages></addata></record> |
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| subjects | alpha-Crystallins - administration & dosage alpha-Crystallins - pharmacology Animals Blotting, Western Cell Survival - drug effects Crystallin Disease Models, Animal Dose-Response Relationship, Drug Female Fluorescent Antibody Technique Injections, Intravenous Male Microglia - drug effects Microglia - metabolism Microscopy, Confocal Microscopy, Fluorescence Nerve Crush Nitric Oxide Synthase Type II - genetics Optic Nerve Injuries - drug therapy Optic Nerve Injuries - pathology Optic nerve injury Rats Rats, Long-Evans Retinal ganglion cell Retinal Ganglion Cells - drug effects Retinal Ganglion Cells - metabolism Retinal microglial activation Time Factors Tumor Necrosis Factor-alpha - genetics |
| title | α-Crystallin protects RGC survival and inhibits microglial activation after optic nerve crush |
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