Effects of aflibercept on primary RPE cells: toxicity, wound healing, uptake and phagocytosis
Background/aim Anti-VEGF treatment is the therapy of choice in age-related macular degeneration, and is also applied in diabetic macular oedema or retinal vein occlusion. Recently, the fusion protein, aflibercept, has been approved for therapeutic use. In this study, we investigate the effects of af...
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| Veröffentlicht in: | British journal of ophthalmology 2014-10, Vol.98 (10), p.1448-1452 |
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| creator | Klettner, Alexa Tahmaz, Nihat Dithmer, Michaela Richert, Elisabeth Roider, Johann |
| description | Background/aim Anti-VEGF treatment is the therapy of choice in age-related macular degeneration, and is also applied in diabetic macular oedema or retinal vein occlusion. Recently, the fusion protein, aflibercept, has been approved for therapeutic use. In this study, we investigate the effects of aflibercept on primary RPE cells. Methods Primary RPE cells were prepared from freshly slaughtered pigs’ eyes. The impact of aflibercept on cell viability was investigated with MTT and trypan blue exclusion assay. The influence of aflibercept on wound healing was assessed with a scratch assay. Intracellular uptake of aflibercept was investigated in immunohistochemistry and its influence on phagocytosis with a phagocytosis assay using opsonised latex beads. Results Aflibercept displays no cytotoxicity on RPE cells but impairs its wound healing ability. It is taken up into RPE cells and can be intracellularly detected for at least 7 days. Intracellular aflibercept impairs the phagocytic capacity of RPE cells. Conclusions Aflibercept interferes with the physiology of RPE cells, as it is taken up into RPE cells, which is accompanied by a reduction of the phagocytic ability. Additionally, it impairs the wound healing capacity of RPE cells. These effects on the physiology of RPE cells may indicate possible side effects. |
| doi_str_mv | 10.1136/bjophthalmol-2014-305105 |
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Recently, the fusion protein, aflibercept, has been approved for therapeutic use. In this study, we investigate the effects of aflibercept on primary RPE cells. Methods Primary RPE cells were prepared from freshly slaughtered pigs’ eyes. The impact of aflibercept on cell viability was investigated with MTT and trypan blue exclusion assay. The influence of aflibercept on wound healing was assessed with a scratch assay. Intracellular uptake of aflibercept was investigated in immunohistochemistry and its influence on phagocytosis with a phagocytosis assay using opsonised latex beads. Results Aflibercept displays no cytotoxicity on RPE cells but impairs its wound healing ability. It is taken up into RPE cells and can be intracellularly detected for at least 7 days. Intracellular aflibercept impairs the phagocytic capacity of RPE cells. Conclusions Aflibercept interferes with the physiology of RPE cells, as it is taken up into RPE cells, which is accompanied by a reduction of the phagocytic ability. Additionally, it impairs the wound healing capacity of RPE cells. These effects on the physiology of RPE cells may indicate possible side effects.</description><identifier>ISSN: 0007-1161</identifier><identifier>EISSN: 1468-2079</identifier><identifier>DOI: 10.1136/bjophthalmol-2014-305105</identifier><identifier>PMID: 25034050</identifier><identifier>CODEN: BJOPAL</identifier><language>eng</language><publisher>England: BMJ Publishing Group LTD</publisher><subject>Angiogenesis Inhibitors - toxicity ; Animals ; Antibodies, Monoclonal, Humanized - toxicity ; Bevacizumab ; Cell Movement - drug effects ; Cell Survival ; Cells, Cultured ; Coloring Agents - metabolism ; Fluorescent Antibody Technique, Indirect ; Macular degeneration ; Microspheres ; Molecular weight ; Phagocytosis - drug effects ; Phenols ; Photoreceptors ; Physiology ; Ranibizumab ; Receptors, Vascular Endothelial Growth Factor - toxicity ; Recombinant Fusion Proteins - toxicity ; Retinal Pigment Epithelium - drug effects ; Retinal Pigment Epithelium - metabolism ; Retinal Pigment Epithelium - pathology ; Signal transduction ; Swine ; Toxicity ; Trypan Blue - metabolism ; Wound healing ; Wound Healing - drug effects</subject><ispartof>British journal of ophthalmology, 2014-10, Vol.98 (10), p.1448-1452</ispartof><rights>Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions</rights><rights>Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.</rights><rights>Copyright: 2014 Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b569t-e0885bda42aab43f9fb4b613bae8b18f2843ae2018d8c84d347269d053dee4223</citedby><cites>FETCH-LOGICAL-b569t-e0885bda42aab43f9fb4b613bae8b18f2843ae2018d8c84d347269d053dee4223</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttp://bjo.bmj.com/content/98/10/1448.full.pdf$$EPDF$$P50$$Gbmj$$H</linktopdf><linktohtml>$$Uhttp://bjo.bmj.com/content/98/10/1448.full$$EHTML$$P50$$Gbmj$$H</linktohtml><link.rule.ids>114,115,314,777,781,3183,23552,27905,27906,77349,77380</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25034050$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Klettner, Alexa</creatorcontrib><creatorcontrib>Tahmaz, Nihat</creatorcontrib><creatorcontrib>Dithmer, Michaela</creatorcontrib><creatorcontrib>Richert, Elisabeth</creatorcontrib><creatorcontrib>Roider, Johann</creatorcontrib><title>Effects of aflibercept on primary RPE cells: toxicity, wound healing, uptake and phagocytosis</title><title>British journal of ophthalmology</title><addtitle>Br J Ophthalmol</addtitle><description>Background/aim Anti-VEGF treatment is the therapy of choice in age-related macular degeneration, and is also applied in diabetic macular oedema or retinal vein occlusion. Recently, the fusion protein, aflibercept, has been approved for therapeutic use. In this study, we investigate the effects of aflibercept on primary RPE cells. Methods Primary RPE cells were prepared from freshly slaughtered pigs’ eyes. The impact of aflibercept on cell viability was investigated with MTT and trypan blue exclusion assay. The influence of aflibercept on wound healing was assessed with a scratch assay. Intracellular uptake of aflibercept was investigated in immunohistochemistry and its influence on phagocytosis with a phagocytosis assay using opsonised latex beads. Results Aflibercept displays no cytotoxicity on RPE cells but impairs its wound healing ability. It is taken up into RPE cells and can be intracellularly detected for at least 7 days. Intracellular aflibercept impairs the phagocytic capacity of RPE cells. Conclusions Aflibercept interferes with the physiology of RPE cells, as it is taken up into RPE cells, which is accompanied by a reduction of the phagocytic ability. Additionally, it impairs the wound healing capacity of RPE cells. These effects on the physiology of RPE cells may indicate possible side effects.</description><subject>Angiogenesis Inhibitors - toxicity</subject><subject>Animals</subject><subject>Antibodies, Monoclonal, Humanized - toxicity</subject><subject>Bevacizumab</subject><subject>Cell Movement - drug effects</subject><subject>Cell Survival</subject><subject>Cells, Cultured</subject><subject>Coloring Agents - metabolism</subject><subject>Fluorescent Antibody Technique, Indirect</subject><subject>Macular degeneration</subject><subject>Microspheres</subject><subject>Molecular weight</subject><subject>Phagocytosis - drug effects</subject><subject>Phenols</subject><subject>Photoreceptors</subject><subject>Physiology</subject><subject>Ranibizumab</subject><subject>Receptors, Vascular Endothelial Growth Factor - toxicity</subject><subject>Recombinant Fusion Proteins - toxicity</subject><subject>Retinal Pigment Epithelium - drug effects</subject><subject>Retinal Pigment Epithelium - metabolism</subject><subject>Retinal Pigment Epithelium - pathology</subject><subject>Signal transduction</subject><subject>Swine</subject><subject>Toxicity</subject><subject>Trypan Blue - metabolism</subject><subject>Wound healing</subject><subject>Wound Healing - drug effects</subject><issn>0007-1161</issn><issn>1468-2079</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNqNkU1LxDAQhoMo7rr6FyTgxcNW89U29SbL-gELiuhRQtImu13bpjYpuv_eLF1FPHkaZnhm5p15AYAYXWBMk0u1tu3Kr2RV2yoiCLOIohijeA-MMUt4KKXZPhgjhNII4wSPwJFz65CSBKeHYERiRBmK0Ri8zo3RuXfQGihNVSrd5br10Daw7cpadhv49DiHua4qdwW9_Szz0m-m8MP2TQFXWlZls5zCvvXyTUMZau1KLm2-8daV7hgcGFk5fbKLE_ByM3-e3UWLh9v72fUiUnGS-UgjzmNVSEakVIyazCimEkyV1FxhbghnVOpwJy94zllBWUqSrEAxLbRmhNAJOB_mtp1977Xzoi7dVrNstO2dwJyScDNjSUDP_qBr23dNUCdwmvIszniaBYoPVN5Z5zptxO4bAiOxtUD8tkBsLRCDBaH1dLegV7Uufhq_fx4AOgCqXv9_7BcBlZZt</recordid><startdate>20141001</startdate><enddate>20141001</enddate><creator>Klettner, Alexa</creator><creator>Tahmaz, Nihat</creator><creator>Dithmer, Michaela</creator><creator>Richert, Elisabeth</creator><creator>Roider, Johann</creator><general>BMJ Publishing Group LTD</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>BTHHO</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7T5</scope><scope>H94</scope></search><sort><creationdate>20141001</creationdate><title>Effects of aflibercept on primary RPE cells: toxicity, wound healing, uptake and phagocytosis</title><author>Klettner, Alexa ; Tahmaz, Nihat ; Dithmer, Michaela ; Richert, Elisabeth ; Roider, Johann</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b569t-e0885bda42aab43f9fb4b613bae8b18f2843ae2018d8c84d347269d053dee4223</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Angiogenesis Inhibitors - toxicity</topic><topic>Animals</topic><topic>Antibodies, Monoclonal, Humanized - toxicity</topic><topic>Bevacizumab</topic><topic>Cell Movement - drug effects</topic><topic>Cell Survival</topic><topic>Cells, Cultured</topic><topic>Coloring Agents - metabolism</topic><topic>Fluorescent Antibody Technique, Indirect</topic><topic>Macular degeneration</topic><topic>Microspheres</topic><topic>Molecular weight</topic><topic>Phagocytosis - drug effects</topic><topic>Phenols</topic><topic>Photoreceptors</topic><topic>Physiology</topic><topic>Ranibizumab</topic><topic>Receptors, Vascular Endothelial Growth Factor - toxicity</topic><topic>Recombinant Fusion Proteins - toxicity</topic><topic>Retinal Pigment Epithelium - drug effects</topic><topic>Retinal Pigment Epithelium - metabolism</topic><topic>Retinal Pigment Epithelium - pathology</topic><topic>Signal transduction</topic><topic>Swine</topic><topic>Toxicity</topic><topic>Trypan Blue - metabolism</topic><topic>Wound healing</topic><topic>Wound Healing - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Klettner, Alexa</creatorcontrib><creatorcontrib>Tahmaz, Nihat</creatorcontrib><creatorcontrib>Dithmer, Michaela</creatorcontrib><creatorcontrib>Richert, Elisabeth</creatorcontrib><creatorcontrib>Roider, Johann</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>BMJ Journals</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>British journal of ophthalmology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Klettner, Alexa</au><au>Tahmaz, Nihat</au><au>Dithmer, Michaela</au><au>Richert, Elisabeth</au><au>Roider, Johann</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of aflibercept on primary RPE cells: toxicity, wound healing, uptake and phagocytosis</atitle><jtitle>British journal of ophthalmology</jtitle><addtitle>Br J Ophthalmol</addtitle><date>2014-10-01</date><risdate>2014</risdate><volume>98</volume><issue>10</issue><spage>1448</spage><epage>1452</epage><pages>1448-1452</pages><issn>0007-1161</issn><eissn>1468-2079</eissn><coden>BJOPAL</coden><abstract>Background/aim Anti-VEGF treatment is the therapy of choice in age-related macular degeneration, and is also applied in diabetic macular oedema or retinal vein occlusion. Recently, the fusion protein, aflibercept, has been approved for therapeutic use. In this study, we investigate the effects of aflibercept on primary RPE cells. Methods Primary RPE cells were prepared from freshly slaughtered pigs’ eyes. The impact of aflibercept on cell viability was investigated with MTT and trypan blue exclusion assay. The influence of aflibercept on wound healing was assessed with a scratch assay. Intracellular uptake of aflibercept was investigated in immunohistochemistry and its influence on phagocytosis with a phagocytosis assay using opsonised latex beads. Results Aflibercept displays no cytotoxicity on RPE cells but impairs its wound healing ability. It is taken up into RPE cells and can be intracellularly detected for at least 7 days. Intracellular aflibercept impairs the phagocytic capacity of RPE cells. Conclusions Aflibercept interferes with the physiology of RPE cells, as it is taken up into RPE cells, which is accompanied by a reduction of the phagocytic ability. Additionally, it impairs the wound healing capacity of RPE cells. These effects on the physiology of RPE cells may indicate possible side effects.</abstract><cop>England</cop><pub>BMJ Publishing Group LTD</pub><pmid>25034050</pmid><doi>10.1136/bjophthalmol-2014-305105</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Angiogenesis Inhibitors - toxicity Animals Antibodies, Monoclonal, Humanized - toxicity Bevacizumab Cell Movement - drug effects Cell Survival Cells, Cultured Coloring Agents - metabolism Fluorescent Antibody Technique, Indirect Macular degeneration Microspheres Molecular weight Phagocytosis - drug effects Phenols Photoreceptors Physiology Ranibizumab Receptors, Vascular Endothelial Growth Factor - toxicity Recombinant Fusion Proteins - toxicity Retinal Pigment Epithelium - drug effects Retinal Pigment Epithelium - metabolism Retinal Pigment Epithelium - pathology Signal transduction Swine Toxicity Trypan Blue - metabolism Wound healing Wound Healing - drug effects |
| title | Effects of aflibercept on primary RPE cells: toxicity, wound healing, uptake and phagocytosis |
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