Adenovirus-mediated delivery of catalase to retinal pigment epithelial cells protects neighboring photoreceptors from photo-oxidative stress
Oxidative stress is involved in the pathogenesis of many diseases. Overexpression of antioxidant enzymes by gene therapy may protect tissues from oxidative damage. Because the reactive oxygen species hydrogen peroxide can diffuse across cell membranes, we hypothesized that overexpression of the anti...
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Veröffentlicht in: | Human gene therapy 2004-10, Vol.15 (10), p.960-967 |
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description | Oxidative stress is involved in the pathogenesis of many diseases. Overexpression of antioxidant enzymes by gene therapy may protect tissues from oxidative damage. Because the reactive oxygen species hydrogen peroxide can diffuse across cell membranes, we hypothesized that overexpression of the antioxidant catalase within certain cells might protect neighboring cells. To test this hypothesis, we transduced retinal pigment epithelial (RPE) cells in vitro and in vivo with adenovirus carrying the catalase gene (Ad.CMV.catalase). After transduction of only a subset of RPE cells in vitro, all cells in the culture were protected from exogenous hydrogen peroxide. Similarly, in vivo, eyes injected with Ad. CMV. catalase had high catalase levels in the RPE, which protected the adjacent photoreceptors from light damage and reduced photoreceptor oxidative stress as measured by the markers 4-hydroxynonenal and nitrotyrosine. Both in vitro and in vivo, gene therapy with Ad. CMV. catalase protected neighboring cells from oxidative stress-induced terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) positivity. The data provide a paradigm for antioxidant gene therapy with catalase, designed to protect not only transduced cells, but also neighboring cells. |
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S ; TSUI, I ; HAHN, P ; MAGUIRE, A. M ; DUAN, D ; BENNETT, J ; DUNAIEF, J. L</creator><creatorcontrib>REX, T. S ; TSUI, I ; HAHN, P ; MAGUIRE, A. M ; DUAN, D ; BENNETT, J ; DUNAIEF, J. L</creatorcontrib><description>Oxidative stress is involved in the pathogenesis of many diseases. Overexpression of antioxidant enzymes by gene therapy may protect tissues from oxidative damage. Because the reactive oxygen species hydrogen peroxide can diffuse across cell membranes, we hypothesized that overexpression of the antioxidant catalase within certain cells might protect neighboring cells. To test this hypothesis, we transduced retinal pigment epithelial (RPE) cells in vitro and in vivo with adenovirus carrying the catalase gene (Ad.CMV.catalase). After transduction of only a subset of RPE cells in vitro, all cells in the culture were protected from exogenous hydrogen peroxide. Similarly, in vivo, eyes injected with Ad. CMV. catalase had high catalase levels in the RPE, which protected the adjacent photoreceptors from light damage and reduced photoreceptor oxidative stress as measured by the markers 4-hydroxynonenal and nitrotyrosine. Both in vitro and in vivo, gene therapy with Ad. CMV. catalase protected neighboring cells from oxidative stress-induced terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) positivity. The data provide a paradigm for antioxidant gene therapy with catalase, designed to protect not only transduced cells, but also neighboring cells.</description><identifier>ISSN: 1043-0342</identifier><identifier>EISSN: 1557-7422</identifier><identifier>DOI: 10.1089/hum.2004.15.960</identifier><identifier>PMID: 15585111</identifier><identifier>CODEN: HGTHE3</identifier><language>eng</language><publisher>Larchmont, NY: Liebert</publisher><subject>Adenoviridae - genetics ; Adenovirus ; Aldehydes - chemistry ; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Animals ; Applied cell therapy and gene therapy ; Biological and medical sciences ; Biotechnology ; Catalase - genetics ; Catalase - metabolism ; Cell Membrane - metabolism ; Fundamental and applied biological sciences. Psychology ; Gene therapy ; Gene Transfer Techniques ; Genetic Therapy - methods ; Health. Pharmaceutical industry ; Humans ; Hydrogen Peroxide - chemistry ; Hydrogen Peroxide - pharmacology ; Immunohistochemistry ; In Situ Nick-End Labeling ; Industrial applications and implications. Economical aspects ; Light ; Male ; Medical sciences ; Mice ; Mice, Inbred BALB C ; Microscopy, Confocal ; Oxidative Stress ; Photoreceptor Cells - metabolism ; Pigment Epithelium of Eye - metabolism ; Retina - metabolism ; Transfusions. Complications. Transfusion reactions. Cell and gene therapy</subject><ispartof>Human gene therapy, 2004-10, Vol.15 (10), p.960-967</ispartof><rights>2004 INIST-CNRS</rights><rights>Mary Ann Liebert, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c450t-b8e4843d0f9976540167d351084551723f727e644ce4c890ca1de1974e7551253</citedby><cites>FETCH-LOGICAL-c450t-b8e4843d0f9976540167d351084551723f727e644ce4c890ca1de1974e7551253</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,3042,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16211762$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15585111$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>REX, T. S</creatorcontrib><creatorcontrib>TSUI, I</creatorcontrib><creatorcontrib>HAHN, P</creatorcontrib><creatorcontrib>MAGUIRE, A. M</creatorcontrib><creatorcontrib>DUAN, D</creatorcontrib><creatorcontrib>BENNETT, J</creatorcontrib><creatorcontrib>DUNAIEF, J. L</creatorcontrib><title>Adenovirus-mediated delivery of catalase to retinal pigment epithelial cells protects neighboring photoreceptors from photo-oxidative stress</title><title>Human gene therapy</title><addtitle>Hum Gene Ther</addtitle><description>Oxidative stress is involved in the pathogenesis of many diseases. Overexpression of antioxidant enzymes by gene therapy may protect tissues from oxidative damage. Because the reactive oxygen species hydrogen peroxide can diffuse across cell membranes, we hypothesized that overexpression of the antioxidant catalase within certain cells might protect neighboring cells. To test this hypothesis, we transduced retinal pigment epithelial (RPE) cells in vitro and in vivo with adenovirus carrying the catalase gene (Ad.CMV.catalase). After transduction of only a subset of RPE cells in vitro, all cells in the culture were protected from exogenous hydrogen peroxide. Similarly, in vivo, eyes injected with Ad. CMV. catalase had high catalase levels in the RPE, which protected the adjacent photoreceptors from light damage and reduced photoreceptor oxidative stress as measured by the markers 4-hydroxynonenal and nitrotyrosine. Both in vitro and in vivo, gene therapy with Ad. CMV. catalase protected neighboring cells from oxidative stress-induced terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) positivity. The data provide a paradigm for antioxidant gene therapy with catalase, designed to protect not only transduced cells, but also neighboring cells.</description><subject>Adenoviridae - genetics</subject><subject>Adenovirus</subject><subject>Aldehydes - chemistry</subject><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>Animals</subject><subject>Applied cell therapy and gene therapy</subject><subject>Biological and medical sciences</subject><subject>Biotechnology</subject><subject>Catalase - genetics</subject><subject>Catalase - metabolism</subject><subject>Cell Membrane - metabolism</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene therapy</subject><subject>Gene Transfer Techniques</subject><subject>Genetic Therapy - methods</subject><subject>Health. Pharmaceutical industry</subject><subject>Humans</subject><subject>Hydrogen Peroxide - chemistry</subject><subject>Hydrogen Peroxide - pharmacology</subject><subject>Immunohistochemistry</subject><subject>In Situ Nick-End Labeling</subject><subject>Industrial applications and implications. Economical aspects</subject><subject>Light</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Microscopy, Confocal</subject><subject>Oxidative Stress</subject><subject>Photoreceptor Cells - metabolism</subject><subject>Pigment Epithelium of Eye - metabolism</subject><subject>Retina - metabolism</subject><subject>Transfusions. Complications. Transfusion reactions. Cell and gene therapy</subject><issn>1043-0342</issn><issn>1557-7422</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU9v1DAQxSNERUvhzA35ArdsPY4dJxekquKfVKmXcra8zmRjlMTB46za78CHxqtdUTj1NNbMz89-84riHfAN8Ka9GtZpIziXG1CbtuYvigtQSpdaCvEyn7msSl5JcV68JvrJOVSq1q-K8ww1CgAuit_XHc5h7-NK5YSdtwk71uHo9xgfWeiZs8mOlpClwCImP9uRLX434ZwYLj4Nmc0th-NIbIkhoUvEZvS7YRuin3dsGUIKER0uuRDrY5iOvTI8-M6m_BSjFJHoTXHW25Hw7aleFj--fL6_-Vbe3n39fnN9WzqpeCq3DcpGVh3v21bXSnKodVepvBCpFGhR9VporKV0KF3TcmehQ2i1RJ3nQlWXxaej7rJus2mXvUQ7miX6ycZHE6w3_09mP5hd2BsJ0IjmIPDxJBDDrxUpmcnTYQV2xrCSqTWolvP2WRC0BpCiyeDVEXQxEEXs__4GuDlEbXLU5hC1AWVy1PnG-39NPPGnbDPw4QRYcnbso52dpyeuFgC6FtUf5NC1_Q</recordid><startdate>20041001</startdate><enddate>20041001</enddate><creator>REX, T. S</creator><creator>TSUI, I</creator><creator>HAHN, P</creator><creator>MAGUIRE, A. M</creator><creator>DUAN, D</creator><creator>BENNETT, J</creator><creator>DUNAIEF, J. L</creator><general>Liebert</general><scope>IQODW</scope><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>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20041001</creationdate><title>Adenovirus-mediated delivery of catalase to retinal pigment epithelial cells protects neighboring photoreceptors from photo-oxidative stress</title><author>REX, T. S ; TSUI, I ; HAHN, P ; MAGUIRE, A. M ; DUAN, D ; BENNETT, J ; DUNAIEF, J. L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c450t-b8e4843d0f9976540167d351084551723f727e644ce4c890ca1de1974e7551253</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Adenoviridae - genetics</topic><topic>Adenovirus</topic><topic>Aldehydes - chemistry</topic><topic>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</topic><topic>Animals</topic><topic>Applied cell therapy and gene therapy</topic><topic>Biological and medical sciences</topic><topic>Biotechnology</topic><topic>Catalase - genetics</topic><topic>Catalase - metabolism</topic><topic>Cell Membrane - metabolism</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene therapy</topic><topic>Gene Transfer Techniques</topic><topic>Genetic Therapy - methods</topic><topic>Health. Pharmaceutical industry</topic><topic>Humans</topic><topic>Hydrogen Peroxide - chemistry</topic><topic>Hydrogen Peroxide - pharmacology</topic><topic>Immunohistochemistry</topic><topic>In Situ Nick-End Labeling</topic><topic>Industrial applications and implications. Economical aspects</topic><topic>Light</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Microscopy, Confocal</topic><topic>Oxidative Stress</topic><topic>Photoreceptor Cells - metabolism</topic><topic>Pigment Epithelium of Eye - metabolism</topic><topic>Retina - metabolism</topic><topic>Transfusions. Complications. Transfusion reactions. Cell and gene therapy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>REX, T. S</creatorcontrib><creatorcontrib>TSUI, I</creatorcontrib><creatorcontrib>HAHN, P</creatorcontrib><creatorcontrib>MAGUIRE, A. M</creatorcontrib><creatorcontrib>DUAN, D</creatorcontrib><creatorcontrib>BENNETT, J</creatorcontrib><creatorcontrib>DUNAIEF, J. L</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Human gene therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>REX, T. S</au><au>TSUI, I</au><au>HAHN, P</au><au>MAGUIRE, A. M</au><au>DUAN, D</au><au>BENNETT, J</au><au>DUNAIEF, J. L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Adenovirus-mediated delivery of catalase to retinal pigment epithelial cells protects neighboring photoreceptors from photo-oxidative stress</atitle><jtitle>Human gene therapy</jtitle><addtitle>Hum Gene Ther</addtitle><date>2004-10-01</date><risdate>2004</risdate><volume>15</volume><issue>10</issue><spage>960</spage><epage>967</epage><pages>960-967</pages><issn>1043-0342</issn><eissn>1557-7422</eissn><coden>HGTHE3</coden><abstract>Oxidative stress is involved in the pathogenesis of many diseases. Overexpression of antioxidant enzymes by gene therapy may protect tissues from oxidative damage. Because the reactive oxygen species hydrogen peroxide can diffuse across cell membranes, we hypothesized that overexpression of the antioxidant catalase within certain cells might protect neighboring cells. To test this hypothesis, we transduced retinal pigment epithelial (RPE) cells in vitro and in vivo with adenovirus carrying the catalase gene (Ad.CMV.catalase). After transduction of only a subset of RPE cells in vitro, all cells in the culture were protected from exogenous hydrogen peroxide. Similarly, in vivo, eyes injected with Ad. CMV. catalase had high catalase levels in the RPE, which protected the adjacent photoreceptors from light damage and reduced photoreceptor oxidative stress as measured by the markers 4-hydroxynonenal and nitrotyrosine. Both in vitro and in vivo, gene therapy with Ad. CMV. catalase protected neighboring cells from oxidative stress-induced terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) positivity. The data provide a paradigm for antioxidant gene therapy with catalase, designed to protect not only transduced cells, but also neighboring cells.</abstract><cop>Larchmont, NY</cop><pub>Liebert</pub><pmid>15585111</pmid><doi>10.1089/hum.2004.15.960</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adenoviridae - genetics Adenovirus Aldehydes - chemistry Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Animals Applied cell therapy and gene therapy Biological and medical sciences Biotechnology Catalase - genetics Catalase - metabolism Cell Membrane - metabolism Fundamental and applied biological sciences. Psychology Gene therapy Gene Transfer Techniques Genetic Therapy - methods Health. Pharmaceutical industry Humans Hydrogen Peroxide - chemistry Hydrogen Peroxide - pharmacology Immunohistochemistry In Situ Nick-End Labeling Industrial applications and implications. Economical aspects Light Male Medical sciences Mice Mice, Inbred BALB C Microscopy, Confocal Oxidative Stress Photoreceptor Cells - metabolism Pigment Epithelium of Eye - metabolism Retina - metabolism Transfusions. Complications. Transfusion reactions. Cell and gene therapy |
title | Adenovirus-mediated delivery of catalase to retinal pigment epithelial cells protects neighboring photoreceptors from photo-oxidative stress |
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