The Use of Adenovirus-Mediated Gene Transfer to Develop a Rat Model for Photoreceptor Degeneration
To investigate the effects of recombinant adenovirus-mediated downregulation of cathepsin S (CatS) on the retinal pigment epithelium and/or neural retina in vivo. The expression of green fluorescent protein (gfp) after subretinal injection of a recombinant adenovirus, Ad.gfp, into rat eyes was first...
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| Veröffentlicht in: | Investigative ophthalmology & visual science 2000-02, Vol.41 (2), p.580-584 |
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| creator | Lai, Chooi-May Shen, Wei-Yong Constable, Ian Rakoczy, Piroska Elizabeth |
| description | To investigate the effects of recombinant adenovirus-mediated downregulation of cathepsin S (CatS) on the retinal pigment epithelium and/or neural retina in vivo.
The expression of green fluorescent protein (gfp) after subretinal injection of a recombinant adenovirus, Ad.gfp, into rat eyes was first established by in vivo fundus fluorescence photography and fluorescence microscopy. The autofluorescent debris accumulation in Ad.CatSAS (recombinant adenovirus carrying the antisense CatS gene)injected rat eyes was monitored by fluorescence microscopy, and the antisense CatS RNA expression was demonstrated by in situ hybridization. Changes in the retinal morphology were assessed by light microscopy. ResuLTS. The gfp expression was present in 30% to 90% of the injection area at 3 days and was absent 9 days after Ad.gfp injection. In Ad.CatSAS-injected eyes, the expression of antisense CatS RNA was demonstrated by in situ hybridization. Autofluorescent debris accumulation was significantly higher in Ad.CatSAS-injected eyes than in control eyes. The shortening of photoreceptor outer segments in Ad.CatSAS-injected eyes coincided with intense autofluorescent debris accumulation. The number of layers of photoreceptor cells decreased with time and were 11, 9, and 8 at 7, 14, and 28 days after Ad.CatSAS injection, respectively. In control eyes, the number of layers of photoreceptor cells (14) remained unchanged.
These results demonstrate that recombinant adenovirus-mediated transient modulation of gene expression in retinal pigment epithelial (RPE) cells could induce changes in the retina, and, in spite of the low expression of endogenous CatS in RPE cells, this enzyme plays an important role in maintenance of normal retinal function. |
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The expression of green fluorescent protein (gfp) after subretinal injection of a recombinant adenovirus, Ad.gfp, into rat eyes was first established by in vivo fundus fluorescence photography and fluorescence microscopy. The autofluorescent debris accumulation in Ad.CatSAS (recombinant adenovirus carrying the antisense CatS gene)injected rat eyes was monitored by fluorescence microscopy, and the antisense CatS RNA expression was demonstrated by in situ hybridization. Changes in the retinal morphology were assessed by light microscopy. ResuLTS. The gfp expression was present in 30% to 90% of the injection area at 3 days and was absent 9 days after Ad.gfp injection. In Ad.CatSAS-injected eyes, the expression of antisense CatS RNA was demonstrated by in situ hybridization. Autofluorescent debris accumulation was significantly higher in Ad.CatSAS-injected eyes than in control eyes. The shortening of photoreceptor outer segments in Ad.CatSAS-injected eyes coincided with intense autofluorescent debris accumulation. The number of layers of photoreceptor cells decreased with time and were 11, 9, and 8 at 7, 14, and 28 days after Ad.CatSAS injection, respectively. In control eyes, the number of layers of photoreceptor cells (14) remained unchanged.
These results demonstrate that recombinant adenovirus-mediated transient modulation of gene expression in retinal pigment epithelial (RPE) cells could induce changes in the retina, and, in spite of the low expression of endogenous CatS in RPE cells, this enzyme plays an important role in maintenance of normal retinal function.</description><identifier>ISSN: 0146-0404</identifier><identifier>EISSN: 1552-5783</identifier><identifier>PMID: 10670491</identifier><identifier>CODEN: IOVSDA</identifier><language>eng</language><publisher>Rockville, MD: ARVO</publisher><subject>Adenoviridae - genetics ; Animals ; Biological and medical sciences ; Cathepsins - genetics ; Cathepsins - metabolism ; Disease Models, Animal ; Down-Regulation ; Fundus Oculi ; Gene Expression ; Gene Transfer Techniques ; Green Fluorescent Proteins ; In Situ Hybridization ; Luminescent Proteins - genetics ; Luminescent Proteins - metabolism ; Medical sciences ; Microscopy, Fluorescence ; Ophthalmology ; Photoreceptor Cells - enzymology ; Photoreceptor Cells - pathology ; Photoreceptor Cells - virology ; Pigment Epithelium of Eye - enzymology ; Pigment Epithelium of Eye - pathology ; Pigment Epithelium of Eye - virology ; Rats ; Rats, Mutant Strains ; Retinal Degeneration - enzymology ; Retinal Degeneration - etiology ; Retinal Degeneration - pathology ; Retinal Degeneration - virology ; Retinopathies</subject><ispartof>Investigative ophthalmology & visual science, 2000-02, Vol.41 (2), p.580-584</ispartof><rights>2000 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1286424$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10670491$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lai, Chooi-May</creatorcontrib><creatorcontrib>Shen, Wei-Yong</creatorcontrib><creatorcontrib>Constable, Ian</creatorcontrib><creatorcontrib>Rakoczy, Piroska Elizabeth</creatorcontrib><title>The Use of Adenovirus-Mediated Gene Transfer to Develop a Rat Model for Photoreceptor Degeneration</title><title>Investigative ophthalmology & visual science</title><addtitle>Invest Ophthalmol Vis Sci</addtitle><description>To investigate the effects of recombinant adenovirus-mediated downregulation of cathepsin S (CatS) on the retinal pigment epithelium and/or neural retina in vivo.
The expression of green fluorescent protein (gfp) after subretinal injection of a recombinant adenovirus, Ad.gfp, into rat eyes was first established by in vivo fundus fluorescence photography and fluorescence microscopy. The autofluorescent debris accumulation in Ad.CatSAS (recombinant adenovirus carrying the antisense CatS gene)injected rat eyes was monitored by fluorescence microscopy, and the antisense CatS RNA expression was demonstrated by in situ hybridization. Changes in the retinal morphology were assessed by light microscopy. ResuLTS. The gfp expression was present in 30% to 90% of the injection area at 3 days and was absent 9 days after Ad.gfp injection. In Ad.CatSAS-injected eyes, the expression of antisense CatS RNA was demonstrated by in situ hybridization. Autofluorescent debris accumulation was significantly higher in Ad.CatSAS-injected eyes than in control eyes. The shortening of photoreceptor outer segments in Ad.CatSAS-injected eyes coincided with intense autofluorescent debris accumulation. The number of layers of photoreceptor cells decreased with time and were 11, 9, and 8 at 7, 14, and 28 days after Ad.CatSAS injection, respectively. In control eyes, the number of layers of photoreceptor cells (14) remained unchanged.
These results demonstrate that recombinant adenovirus-mediated transient modulation of gene expression in retinal pigment epithelial (RPE) cells could induce changes in the retina, and, in spite of the low expression of endogenous CatS in RPE cells, this enzyme plays an important role in maintenance of normal retinal function.</description><subject>Adenoviridae - genetics</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cathepsins - genetics</subject><subject>Cathepsins - metabolism</subject><subject>Disease Models, Animal</subject><subject>Down-Regulation</subject><subject>Fundus Oculi</subject><subject>Gene Expression</subject><subject>Gene Transfer Techniques</subject><subject>Green Fluorescent Proteins</subject><subject>In Situ Hybridization</subject><subject>Luminescent Proteins - genetics</subject><subject>Luminescent Proteins - metabolism</subject><subject>Medical sciences</subject><subject>Microscopy, Fluorescence</subject><subject>Ophthalmology</subject><subject>Photoreceptor Cells - enzymology</subject><subject>Photoreceptor Cells - pathology</subject><subject>Photoreceptor Cells - virology</subject><subject>Pigment Epithelium of Eye - enzymology</subject><subject>Pigment Epithelium of Eye - pathology</subject><subject>Pigment Epithelium of Eye - virology</subject><subject>Rats</subject><subject>Rats, Mutant Strains</subject><subject>Retinal Degeneration - enzymology</subject><subject>Retinal Degeneration - etiology</subject><subject>Retinal Degeneration - pathology</subject><subject>Retinal Degeneration - virology</subject><subject>Retinopathies</subject><issn>0146-0404</issn><issn>1552-5783</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpF0M1Kw0AUBeAgiq3VV5BZqLvA_CdZlqpVaFGkXQ-T5KaJTDJxJmnw7R2w4upsvnvg3LNoToSgsUhSdh7NMeEyxhzzWXTl_SfGlBCKL6MZwTLBPCPzKN_VgPYekK3QsoTOHhs3-ngLZaMHKNEaOkA7pztfgUODRY9wBGN7pNGHHtDWlmBQZR16r-1gHRTQhwjqEA6dHhrbXUcXlTYebk65iPbPT7vVS7x5W7-ulpu4plIOMRCWcy5BY14JwrOSpSlmPC0oFWVSJBIkTiGRucwY5YkuilSwPEnzSggiANgievjt7Z39GsEPqm18AcboDuzoVYKzsFmyAG9PcMxbKFXvmla7b_X3lQDuTkD7QpsqzC8a_-9oKjnlgd3_sro51FPjQPlWGxNaiZqmiRNFlQgbfgA_e3fE</recordid><startdate>20000201</startdate><enddate>20000201</enddate><creator>Lai, Chooi-May</creator><creator>Shen, Wei-Yong</creator><creator>Constable, Ian</creator><creator>Rakoczy, Piroska Elizabeth</creator><general>ARVO</general><general>Association for Research in Vision and Ophtalmology</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>20000201</creationdate><title>The Use of Adenovirus-Mediated Gene Transfer to Develop a Rat Model for Photoreceptor Degeneration</title><author>Lai, Chooi-May ; Shen, Wei-Yong ; Constable, Ian ; Rakoczy, Piroska Elizabeth</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h266t-e13b446ea04f5149d3880348c225d7c76e608e76b693247acc853b78bf5515ee3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Adenoviridae - genetics</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cathepsins - genetics</topic><topic>Cathepsins - metabolism</topic><topic>Disease Models, Animal</topic><topic>Down-Regulation</topic><topic>Fundus Oculi</topic><topic>Gene Expression</topic><topic>Gene Transfer Techniques</topic><topic>Green Fluorescent Proteins</topic><topic>In Situ Hybridization</topic><topic>Luminescent Proteins - genetics</topic><topic>Luminescent Proteins - metabolism</topic><topic>Medical sciences</topic><topic>Microscopy, Fluorescence</topic><topic>Ophthalmology</topic><topic>Photoreceptor Cells - enzymology</topic><topic>Photoreceptor Cells - pathology</topic><topic>Photoreceptor Cells - virology</topic><topic>Pigment Epithelium of Eye - enzymology</topic><topic>Pigment Epithelium of Eye - pathology</topic><topic>Pigment Epithelium of Eye - virology</topic><topic>Rats</topic><topic>Rats, Mutant Strains</topic><topic>Retinal Degeneration - enzymology</topic><topic>Retinal Degeneration - etiology</topic><topic>Retinal Degeneration - pathology</topic><topic>Retinal Degeneration - virology</topic><topic>Retinopathies</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lai, Chooi-May</creatorcontrib><creatorcontrib>Shen, Wei-Yong</creatorcontrib><creatorcontrib>Constable, Ian</creatorcontrib><creatorcontrib>Rakoczy, Piroska Elizabeth</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>MEDLINE - Academic</collection><jtitle>Investigative ophthalmology & visual science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lai, Chooi-May</au><au>Shen, Wei-Yong</au><au>Constable, Ian</au><au>Rakoczy, Piroska Elizabeth</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Use of Adenovirus-Mediated Gene Transfer to Develop a Rat Model for Photoreceptor Degeneration</atitle><jtitle>Investigative ophthalmology & visual science</jtitle><addtitle>Invest Ophthalmol Vis Sci</addtitle><date>2000-02-01</date><risdate>2000</risdate><volume>41</volume><issue>2</issue><spage>580</spage><epage>584</epage><pages>580-584</pages><issn>0146-0404</issn><eissn>1552-5783</eissn><coden>IOVSDA</coden><abstract>To investigate the effects of recombinant adenovirus-mediated downregulation of cathepsin S (CatS) on the retinal pigment epithelium and/or neural retina in vivo.
The expression of green fluorescent protein (gfp) after subretinal injection of a recombinant adenovirus, Ad.gfp, into rat eyes was first established by in vivo fundus fluorescence photography and fluorescence microscopy. The autofluorescent debris accumulation in Ad.CatSAS (recombinant adenovirus carrying the antisense CatS gene)injected rat eyes was monitored by fluorescence microscopy, and the antisense CatS RNA expression was demonstrated by in situ hybridization. Changes in the retinal morphology were assessed by light microscopy. ResuLTS. The gfp expression was present in 30% to 90% of the injection area at 3 days and was absent 9 days after Ad.gfp injection. In Ad.CatSAS-injected eyes, the expression of antisense CatS RNA was demonstrated by in situ hybridization. Autofluorescent debris accumulation was significantly higher in Ad.CatSAS-injected eyes than in control eyes. The shortening of photoreceptor outer segments in Ad.CatSAS-injected eyes coincided with intense autofluorescent debris accumulation. The number of layers of photoreceptor cells decreased with time and were 11, 9, and 8 at 7, 14, and 28 days after Ad.CatSAS injection, respectively. In control eyes, the number of layers of photoreceptor cells (14) remained unchanged.
These results demonstrate that recombinant adenovirus-mediated transient modulation of gene expression in retinal pigment epithelial (RPE) cells could induce changes in the retina, and, in spite of the low expression of endogenous CatS in RPE cells, this enzyme plays an important role in maintenance of normal retinal function.</abstract><cop>Rockville, MD</cop><pub>ARVO</pub><pmid>10670491</pmid><tpages>5</tpages></addata></record> |
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| subjects | Adenoviridae - genetics Animals Biological and medical sciences Cathepsins - genetics Cathepsins - metabolism Disease Models, Animal Down-Regulation Fundus Oculi Gene Expression Gene Transfer Techniques Green Fluorescent Proteins In Situ Hybridization Luminescent Proteins - genetics Luminescent Proteins - metabolism Medical sciences Microscopy, Fluorescence Ophthalmology Photoreceptor Cells - enzymology Photoreceptor Cells - pathology Photoreceptor Cells - virology Pigment Epithelium of Eye - enzymology Pigment Epithelium of Eye - pathology Pigment Epithelium of Eye - virology Rats Rats, Mutant Strains Retinal Degeneration - enzymology Retinal Degeneration - etiology Retinal Degeneration - pathology Retinal Degeneration - virology Retinopathies |
| title | The Use of Adenovirus-Mediated Gene Transfer to Develop a Rat Model for Photoreceptor Degeneration |
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