Local partial depletion of CD11b+ cells and their influence on choroidal neovascularization using the CD11b‐HSVTK mouse model
Purpose To assess the influence of retinal macrophages and microglia on the formation of choroidal neovascularization (CNV). Therefore, we used a transgenic mouse (CD11b‐HSVTK) in which the application of ganciclovir (GCV) results in a depletion of CD11b+ cells. Methods We first investigated if a lo...
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| creator | Brockmann, Claudia Kociok, Norbert Dege, Sabrina Davids, Anja‐Maria Brockmann, Tobias Miller, Kelly R. Joussen, Antonia M. |
| description | Purpose
To assess the influence of retinal macrophages and microglia on the formation of choroidal neovascularization (CNV). Therefore, we used a transgenic mouse (CD11b‐HSVTK) in which the application of ganciclovir (GCV) results in a depletion of CD11b+ cells.
Methods
We first investigated if a local depletion of CD11b+ macrophages and microglia in the retina is feasible. In a second step, the influence of CD11b+ cell depletion on CNV formation was analysed. One eye of each CD11b‐HSVTK mouse was injected with GCV, and the fellow eye received sodium chloride solution (NaCl). Cell counting was performed at day 3 and 7 (one injection) or at day 14 and 21 (two injections). Choroidal neovascularization (CNV) was induced by argon laser and analysed at day 14.
Results
The most effective CD11b+ cell depletion was achieved 7 days after a single injection and 14 days after two injections of GCV. After two injections of GCV, we found a significant reduction of CD11b+ cells in central (52 ± 23.9 cells/mm2) and peripheral retina (53 ± 20.6 cells/mm2); compared to eyes received NaCl (216 ± 49.0 and 210 ± 50.5 cells/mm2, p |
| doi_str_mv | 10.1111/aos.13716 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_2013787074</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2013787074</sourcerecordid><originalsourceid>FETCH-LOGICAL-p2866-a892cdffdc0c03a7d3ded8d8b6357fcfe4a37aeb60de3d51f114fb9c9cc840f83</originalsourceid><addsrcrecordid>eNo9kUtOwzAQhi0EgvJYcAHkJRIq2HVip8uqPIqoxKIFsYscewxGThziBFQ2cATOyElwW2AWMyP5m1_j-RE6pOSUxjiTPpxSJijfQD0q0rTPBM82__v0YQfthvBMCKecJ9toZzBMGeep6KGPqVfS4Vo2rY1VQ-2gtb7C3uDxOaXFCVbgXMCy0rh9AttgWxnXQaUAR0w9-cZbHUcr8K8yqM7Jxr7LlUYXbPW4nFpLfX9-TWb38xtc-i5AzBrcPtoy0gU4-K176O7yYj6e9Ke3V9fj0bRfDzLO-zIbDpQ2RiuiCJNCMw0601nBWSqMMpBIJiQUnGhgOqWG0sQUQzVUKkuIydgeOl7r1o1_6SC0eWnD8mcy7t2FfEDiATNBRBLRo1-0K0rQed3YUjaL_O9oEThbA2_WweL_nZJ86UYe3chXbuSj29mqYT8zZn8k</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2013787074</pqid></control><display><type>article</type><title>Local partial depletion of CD11b+ cells and their influence on choroidal neovascularization using the CD11b‐HSVTK mouse model</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><source>Wiley Free Content</source><creator>Brockmann, Claudia ; Kociok, Norbert ; Dege, Sabrina ; Davids, Anja‐Maria ; Brockmann, Tobias ; Miller, Kelly R. ; Joussen, Antonia M.</creator><creatorcontrib>Brockmann, Claudia ; Kociok, Norbert ; Dege, Sabrina ; Davids, Anja‐Maria ; Brockmann, Tobias ; Miller, Kelly R. ; Joussen, Antonia M.</creatorcontrib><description>Purpose
To assess the influence of retinal macrophages and microglia on the formation of choroidal neovascularization (CNV). Therefore, we used a transgenic mouse (CD11b‐HSVTK) in which the application of ganciclovir (GCV) results in a depletion of CD11b+ cells.
Methods
We first investigated if a local depletion of CD11b+ macrophages and microglia in the retina is feasible. In a second step, the influence of CD11b+ cell depletion on CNV formation was analysed. One eye of each CD11b‐HSVTK mouse was injected with GCV, and the fellow eye received sodium chloride solution (NaCl). Cell counting was performed at day 3 and 7 (one injection) or at day 14 and 21 (two injections). Choroidal neovascularization (CNV) was induced by argon laser and analysed at day 14.
Results
The most effective CD11b+ cell depletion was achieved 7 days after a single injection and 14 days after two injections of GCV. After two injections of GCV, we found a significant reduction of CD11b+ cells in central (52 ± 23.9 cells/mm2) and peripheral retina (53 ± 20.6 cells/mm2); compared to eyes received NaCl (216 ± 49.0 and 210 ± 50.5 cells/mm2, p < 0.001, respectively). Regarding CNV areas, no statistical significance was found between the groups.
Conclusion
The CD11b‐HSVTK mouse is a feasible model for a local depletion of CD11b+ cells in the retina. Nevertheless, only a partial depletion of CD11b+ cells could be achieved compared to baseline data without any intravitreal injections. Our results did not reveal a significant reduction in CNV areas. In the light of previous knowledge, the potential influence of systemic immune cells on CNV formation might be more relevant than expected.</description><identifier>ISSN: 1755-375X</identifier><identifier>EISSN: 1755-3768</identifier><identifier>DOI: 10.1111/aos.13716</identifier><identifier>PMID: 29536657</identifier><language>eng</language><publisher>England</publisher><subject>Animals ; Antiviral Agents - pharmacology ; Calcium-Binding Proteins - physiology ; CD11b ; CD11b Antigen - physiology ; Cell Count ; Choroidal Neovascularization - metabolism ; Choroidal Neovascularization - physiopathology ; Disease Models, Animal ; Female ; Ganciclovir - pharmacology ; HSVTK ; intravitreal injection ; Intravitreal Injections ; Laser Coagulation ; laser‐induced neovascularization ; macrophages ; Macrophages - immunology ; Macrophages - pathology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Microfilament Proteins - physiology ; microglia ; Microglia - immunology ; Microglia - pathology ; Polymerase Chain Reaction ; Simplexvirus - enzymology ; Thymidine Kinase - genetics</subject><ispartof>Acta ophthalmologica (Oxford, England), 2018-11, Vol.96 (7), p.e789-e796</ispartof><rights>2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd</rights><rights>2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><orcidid>0000-0002-4753-3045 ; 0000-0003-0904-8177</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Faos.13716$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Faos.13716$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,1433,27924,27925,45574,45575,46409,46833</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29536657$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Brockmann, Claudia</creatorcontrib><creatorcontrib>Kociok, Norbert</creatorcontrib><creatorcontrib>Dege, Sabrina</creatorcontrib><creatorcontrib>Davids, Anja‐Maria</creatorcontrib><creatorcontrib>Brockmann, Tobias</creatorcontrib><creatorcontrib>Miller, Kelly R.</creatorcontrib><creatorcontrib>Joussen, Antonia M.</creatorcontrib><title>Local partial depletion of CD11b+ cells and their influence on choroidal neovascularization using the CD11b‐HSVTK mouse model</title><title>Acta ophthalmologica (Oxford, England)</title><addtitle>Acta Ophthalmol</addtitle><description>Purpose
To assess the influence of retinal macrophages and microglia on the formation of choroidal neovascularization (CNV). Therefore, we used a transgenic mouse (CD11b‐HSVTK) in which the application of ganciclovir (GCV) results in a depletion of CD11b+ cells.
Methods
We first investigated if a local depletion of CD11b+ macrophages and microglia in the retina is feasible. In a second step, the influence of CD11b+ cell depletion on CNV formation was analysed. One eye of each CD11b‐HSVTK mouse was injected with GCV, and the fellow eye received sodium chloride solution (NaCl). Cell counting was performed at day 3 and 7 (one injection) or at day 14 and 21 (two injections). Choroidal neovascularization (CNV) was induced by argon laser and analysed at day 14.
Results
The most effective CD11b+ cell depletion was achieved 7 days after a single injection and 14 days after two injections of GCV. After two injections of GCV, we found a significant reduction of CD11b+ cells in central (52 ± 23.9 cells/mm2) and peripheral retina (53 ± 20.6 cells/mm2); compared to eyes received NaCl (216 ± 49.0 and 210 ± 50.5 cells/mm2, p < 0.001, respectively). Regarding CNV areas, no statistical significance was found between the groups.
Conclusion
The CD11b‐HSVTK mouse is a feasible model for a local depletion of CD11b+ cells in the retina. Nevertheless, only a partial depletion of CD11b+ cells could be achieved compared to baseline data without any intravitreal injections. Our results did not reveal a significant reduction in CNV areas. In the light of previous knowledge, the potential influence of systemic immune cells on CNV formation might be more relevant than expected.</description><subject>Animals</subject><subject>Antiviral Agents - pharmacology</subject><subject>Calcium-Binding Proteins - physiology</subject><subject>CD11b</subject><subject>CD11b Antigen - physiology</subject><subject>Cell Count</subject><subject>Choroidal Neovascularization - metabolism</subject><subject>Choroidal Neovascularization - physiopathology</subject><subject>Disease Models, Animal</subject><subject>Female</subject><subject>Ganciclovir - pharmacology</subject><subject>HSVTK</subject><subject>intravitreal injection</subject><subject>Intravitreal Injections</subject><subject>Laser Coagulation</subject><subject>laser‐induced neovascularization</subject><subject>macrophages</subject><subject>Macrophages - immunology</subject><subject>Macrophages - pathology</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Transgenic</subject><subject>Microfilament Proteins - physiology</subject><subject>microglia</subject><subject>Microglia - immunology</subject><subject>Microglia - pathology</subject><subject>Polymerase Chain Reaction</subject><subject>Simplexvirus - enzymology</subject><subject>Thymidine Kinase - genetics</subject><issn>1755-375X</issn><issn>1755-3768</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kUtOwzAQhi0EgvJYcAHkJRIq2HVip8uqPIqoxKIFsYscewxGThziBFQ2cATOyElwW2AWMyP5m1_j-RE6pOSUxjiTPpxSJijfQD0q0rTPBM82__v0YQfthvBMCKecJ9toZzBMGeep6KGPqVfS4Vo2rY1VQ-2gtb7C3uDxOaXFCVbgXMCy0rh9AttgWxnXQaUAR0w9-cZbHUcr8K8yqM7Jxr7LlUYXbPW4nFpLfX9-TWb38xtc-i5AzBrcPtoy0gU4-K176O7yYj6e9Ke3V9fj0bRfDzLO-zIbDpQ2RiuiCJNCMw0601nBWSqMMpBIJiQUnGhgOqWG0sQUQzVUKkuIydgeOl7r1o1_6SC0eWnD8mcy7t2FfEDiATNBRBLRo1-0K0rQed3YUjaL_O9oEThbA2_WweL_nZJ86UYe3chXbuSj29mqYT8zZn8k</recordid><startdate>201811</startdate><enddate>201811</enddate><creator>Brockmann, Claudia</creator><creator>Kociok, Norbert</creator><creator>Dege, Sabrina</creator><creator>Davids, Anja‐Maria</creator><creator>Brockmann, Tobias</creator><creator>Miller, Kelly R.</creator><creator>Joussen, Antonia M.</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-4753-3045</orcidid><orcidid>https://orcid.org/0000-0003-0904-8177</orcidid></search><sort><creationdate>201811</creationdate><title>Local partial depletion of CD11b+ cells and their influence on choroidal neovascularization using the CD11b‐HSVTK mouse model</title><author>Brockmann, Claudia ; Kociok, Norbert ; Dege, Sabrina ; Davids, Anja‐Maria ; Brockmann, Tobias ; Miller, Kelly R. ; Joussen, Antonia M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p2866-a892cdffdc0c03a7d3ded8d8b6357fcfe4a37aeb60de3d51f114fb9c9cc840f83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Animals</topic><topic>Antiviral Agents - pharmacology</topic><topic>Calcium-Binding Proteins - physiology</topic><topic>CD11b</topic><topic>CD11b Antigen - physiology</topic><topic>Cell Count</topic><topic>Choroidal Neovascularization - metabolism</topic><topic>Choroidal Neovascularization - physiopathology</topic><topic>Disease Models, Animal</topic><topic>Female</topic><topic>Ganciclovir - pharmacology</topic><topic>HSVTK</topic><topic>intravitreal injection</topic><topic>Intravitreal Injections</topic><topic>Laser Coagulation</topic><topic>laser‐induced neovascularization</topic><topic>macrophages</topic><topic>Macrophages - immunology</topic><topic>Macrophages - pathology</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Transgenic</topic><topic>Microfilament Proteins - physiology</topic><topic>microglia</topic><topic>Microglia - immunology</topic><topic>Microglia - pathology</topic><topic>Polymerase Chain Reaction</topic><topic>Simplexvirus - enzymology</topic><topic>Thymidine Kinase - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Brockmann, Claudia</creatorcontrib><creatorcontrib>Kociok, Norbert</creatorcontrib><creatorcontrib>Dege, Sabrina</creatorcontrib><creatorcontrib>Davids, Anja‐Maria</creatorcontrib><creatorcontrib>Brockmann, Tobias</creatorcontrib><creatorcontrib>Miller, Kelly R.</creatorcontrib><creatorcontrib>Joussen, Antonia M.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Acta ophthalmologica (Oxford, England)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Brockmann, Claudia</au><au>Kociok, Norbert</au><au>Dege, Sabrina</au><au>Davids, Anja‐Maria</au><au>Brockmann, Tobias</au><au>Miller, Kelly R.</au><au>Joussen, Antonia M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Local partial depletion of CD11b+ cells and their influence on choroidal neovascularization using the CD11b‐HSVTK mouse model</atitle><jtitle>Acta ophthalmologica (Oxford, England)</jtitle><addtitle>Acta Ophthalmol</addtitle><date>2018-11</date><risdate>2018</risdate><volume>96</volume><issue>7</issue><spage>e789</spage><epage>e796</epage><pages>e789-e796</pages><issn>1755-375X</issn><eissn>1755-3768</eissn><abstract>Purpose
To assess the influence of retinal macrophages and microglia on the formation of choroidal neovascularization (CNV). Therefore, we used a transgenic mouse (CD11b‐HSVTK) in which the application of ganciclovir (GCV) results in a depletion of CD11b+ cells.
Methods
We first investigated if a local depletion of CD11b+ macrophages and microglia in the retina is feasible. In a second step, the influence of CD11b+ cell depletion on CNV formation was analysed. One eye of each CD11b‐HSVTK mouse was injected with GCV, and the fellow eye received sodium chloride solution (NaCl). Cell counting was performed at day 3 and 7 (one injection) or at day 14 and 21 (two injections). Choroidal neovascularization (CNV) was induced by argon laser and analysed at day 14.
Results
The most effective CD11b+ cell depletion was achieved 7 days after a single injection and 14 days after two injections of GCV. After two injections of GCV, we found a significant reduction of CD11b+ cells in central (52 ± 23.9 cells/mm2) and peripheral retina (53 ± 20.6 cells/mm2); compared to eyes received NaCl (216 ± 49.0 and 210 ± 50.5 cells/mm2, p < 0.001, respectively). Regarding CNV areas, no statistical significance was found between the groups.
Conclusion
The CD11b‐HSVTK mouse is a feasible model for a local depletion of CD11b+ cells in the retina. Nevertheless, only a partial depletion of CD11b+ cells could be achieved compared to baseline data without any intravitreal injections. Our results did not reveal a significant reduction in CNV areas. In the light of previous knowledge, the potential influence of systemic immune cells on CNV formation might be more relevant than expected.</abstract><cop>England</cop><pmid>29536657</pmid><doi>10.1111/aos.13716</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-4753-3045</orcidid><orcidid>https://orcid.org/0000-0003-0904-8177</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Antiviral Agents - pharmacology Calcium-Binding Proteins - physiology CD11b CD11b Antigen - physiology Cell Count Choroidal Neovascularization - metabolism Choroidal Neovascularization - physiopathology Disease Models, Animal Female Ganciclovir - pharmacology HSVTK intravitreal injection Intravitreal Injections Laser Coagulation laser‐induced neovascularization macrophages Macrophages - immunology Macrophages - pathology Male Mice Mice, Inbred C57BL Mice, Transgenic Microfilament Proteins - physiology microglia Microglia - immunology Microglia - pathology Polymerase Chain Reaction Simplexvirus - enzymology Thymidine Kinase - genetics |
| title | Local partial depletion of CD11b+ cells and their influence on choroidal neovascularization using the CD11b‐HSVTK mouse model |
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