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Interleukin-10 Gene Transfer in Rat Limbal Transplantation
Purpose: To evaluate the gene transfer of the interleukin (IL)-10 cytokine as a treatment modality for prolonging limbal allograft survival in a rat model. Materials and methods: Adenoviral (AV) and lentiviral (LV) vectors were produced for ex vivo gene transfer into limbal graft tissue prior to ort...
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| Published in: | Current eye research 2017-11, Vol.42 (11), p.1426-1434 |
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| container_end_page | 1434 |
| container_issue | 11 |
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| container_title | Current eye research |
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| creator | Kaufmann, Claude Mortimer, Lauren A Brereton, Helen M Irani, Yazad D Parker, Douglas GA Anson, Donald S Bachmann, Lucas M Williams, Keryn A |
| description | Purpose: To evaluate the gene transfer of the interleukin (IL)-10 cytokine as a treatment modality for prolonging limbal allograft survival in a rat model.
Materials and methods: Adenoviral (AV) and lentiviral (LV) vectors were produced for ex vivo gene transfer into limbal graft tissue prior to orthotopic transplantation. Experimental groups comprised unmodified isografts, unmodified allografts, allografts transfected with a reporter gene, and allografts transfected with IL-10. The functional effects of the transgenes were determined by clinical assessment and by following donor cell survival in the recipient animal. Group comparisons were made using survival analysis and tested with the log-rank test. Differences in mean rejection times between groups were tested using the Wilcoxon rank-sum test.
Results: Isografts survived during the entire observation period of 56 days. Allografts underwent clinical rejection at a mean of 6.7 days (standard deviation 2.0) postoperatively, irrespective of the presence of transgenes (p |
| doi_str_mv | 10.1080/02713683.2017.1344714 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_infor</sourceid><recordid>TN_cdi_proquest_miscellaneous_1940595525</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1940595525</sourcerecordid><originalsourceid>FETCH-LOGICAL-c366t-2cbb4b97cb28656b5e43759e0bb58bf5aaee064edefad7ea94d0fe0e61a2aeba3</originalsourceid><addsrcrecordid>eNp9kE1Lw0AQhhdRbK3-BCVHL6n7ncSTUrQWCoLU87KbzMJqsqm7CdJ_b0KqR08DL887MzwIXRO8JDjHd5hmhMmcLSkm2ZIwzjPCT9CccIlTSjE9RfORSUdohi5i_MB4DPg5mtG8oCJjdI7uN76DUEP_6XxKcLIGD8kuaB8thMT55E13ydY1RtdTvK-173TnWn-JzqyuI1wd5wK9Pz_tVi_p9nW9WT1u05JJ2aW0NIabIisNzaWQRgBnmSgAGyNyY4XWAFhyqMDqKgNd8ApbwCCJphqMZgt0O-3dh_arh9ipxsUS6uERaPuoSMGxKISgYkDFhJahjTGAVfvgGh0OimA1alO_2tSoTR21Db2b44neNFD9tX49DcDDBDhv29Do7zbUler0oW6DHbSULir2_40fHcV8MA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1940595525</pqid></control><display><type>article</type><title>Interleukin-10 Gene Transfer in Rat Limbal Transplantation</title><source>Taylor and Francis:Jisc Collections:Taylor and Francis Read and Publish Agreement 2024-2025:Medical Collection (Reading list)</source><creator>Kaufmann, Claude ; Mortimer, Lauren A ; Brereton, Helen M ; Irani, Yazad D ; Parker, Douglas GA ; Anson, Donald S ; Bachmann, Lucas M ; Williams, Keryn A</creator><creatorcontrib>Kaufmann, Claude ; Mortimer, Lauren A ; Brereton, Helen M ; Irani, Yazad D ; Parker, Douglas GA ; Anson, Donald S ; Bachmann, Lucas M ; Williams, Keryn A</creatorcontrib><description>Purpose: To evaluate the gene transfer of the interleukin (IL)-10 cytokine as a treatment modality for prolonging limbal allograft survival in a rat model.
Materials and methods: Adenoviral (AV) and lentiviral (LV) vectors were produced for ex vivo gene transfer into limbal graft tissue prior to orthotopic transplantation. Experimental groups comprised unmodified isografts, unmodified allografts, allografts transfected with a reporter gene, and allografts transfected with IL-10. The functional effects of the transgenes were determined by clinical assessment and by following donor cell survival in the recipient animal. Group comparisons were made using survival analysis and tested with the log-rank test. Differences in mean rejection times between groups were tested using the Wilcoxon rank-sum test.
Results: Isografts survived during the entire observation period of 56 days. Allografts underwent clinical rejection at a mean of 6.7 days (standard deviation 2.0) postoperatively, irrespective of the presence of transgenes (p < 0.001 for difference in rejection times). For both the AV and LV vector systems, Kaplan-Meier analysis showed a statistically significant difference with respect to time-to-graft failure when comparing allografts transfected with IL-10 with allografts transfected with reporter gene alone (p = 0.011 and p < 0.001, respectively). In the isografts, donor cells could be detected during the complete observation period. In all the allograft groups, however, donor cell detection declined after 1 week and was lost after 4 weeks.
Conclusions: Under the conditions tested in the present model, both the AV and the LV vector systems were able to transfect limbal graft tissue ex vivo with biologically active IL-10, leading to delayed rejection compared to the controls.</description><identifier>ISSN: 0271-3683</identifier><identifier>EISSN: 1460-2202</identifier><identifier>DOI: 10.1080/02713683.2017.1344714</identifier><identifier>PMID: 28925732</identifier><language>eng</language><publisher>England: Taylor & Francis</publisher><subject>Adenoviral vector ; Animals ; Cells, Cultured ; Corneal Diseases - pathology ; Corneal Diseases - surgery ; Corneal Transplantation - methods ; Disease Models, Animal ; Enzyme-Linked Immunosorbent Assay ; Follow-Up Studies ; Gene Expression Regulation ; gene therapy ; Gene Transfer Techniques ; Graft Rejection - genetics ; Graft Rejection - pathology ; Graft Rejection - prevention & control ; Graft Survival - genetics ; interleukin-10 ; Interleukin-10 - biosynthesis ; Interleukin-10 - genetics ; lentiviral vector ; limbal transplantation ; Limbus Corneae - cytology ; Limbus Corneae - surgery ; Rats ; Rats, Inbred F344 ; Rats, Inbred WF ; Reverse Transcriptase Polymerase Chain Reaction ; RNA - genetics ; Transplantation, Homologous</subject><ispartof>Current eye research, 2017-11, Vol.42 (11), p.1426-1434</ispartof><rights>2017 Taylor & Francis 2017</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c366t-2cbb4b97cb28656b5e43759e0bb58bf5aaee064edefad7ea94d0fe0e61a2aeba3</citedby><cites>FETCH-LOGICAL-c366t-2cbb4b97cb28656b5e43759e0bb58bf5aaee064edefad7ea94d0fe0e61a2aeba3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28925732$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kaufmann, Claude</creatorcontrib><creatorcontrib>Mortimer, Lauren A</creatorcontrib><creatorcontrib>Brereton, Helen M</creatorcontrib><creatorcontrib>Irani, Yazad D</creatorcontrib><creatorcontrib>Parker, Douglas GA</creatorcontrib><creatorcontrib>Anson, Donald S</creatorcontrib><creatorcontrib>Bachmann, Lucas M</creatorcontrib><creatorcontrib>Williams, Keryn A</creatorcontrib><title>Interleukin-10 Gene Transfer in Rat Limbal Transplantation</title><title>Current eye research</title><addtitle>Curr Eye Res</addtitle><description>Purpose: To evaluate the gene transfer of the interleukin (IL)-10 cytokine as a treatment modality for prolonging limbal allograft survival in a rat model.
Materials and methods: Adenoviral (AV) and lentiviral (LV) vectors were produced for ex vivo gene transfer into limbal graft tissue prior to orthotopic transplantation. Experimental groups comprised unmodified isografts, unmodified allografts, allografts transfected with a reporter gene, and allografts transfected with IL-10. The functional effects of the transgenes were determined by clinical assessment and by following donor cell survival in the recipient animal. Group comparisons were made using survival analysis and tested with the log-rank test. Differences in mean rejection times between groups were tested using the Wilcoxon rank-sum test.
Results: Isografts survived during the entire observation period of 56 days. Allografts underwent clinical rejection at a mean of 6.7 days (standard deviation 2.0) postoperatively, irrespective of the presence of transgenes (p < 0.001 for difference in rejection times). For both the AV and LV vector systems, Kaplan-Meier analysis showed a statistically significant difference with respect to time-to-graft failure when comparing allografts transfected with IL-10 with allografts transfected with reporter gene alone (p = 0.011 and p < 0.001, respectively). In the isografts, donor cells could be detected during the complete observation period. In all the allograft groups, however, donor cell detection declined after 1 week and was lost after 4 weeks.
Conclusions: Under the conditions tested in the present model, both the AV and the LV vector systems were able to transfect limbal graft tissue ex vivo with biologically active IL-10, leading to delayed rejection compared to the controls.</description><subject>Adenoviral vector</subject><subject>Animals</subject><subject>Cells, Cultured</subject><subject>Corneal Diseases - pathology</subject><subject>Corneal Diseases - surgery</subject><subject>Corneal Transplantation - methods</subject><subject>Disease Models, Animal</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Follow-Up Studies</subject><subject>Gene Expression Regulation</subject><subject>gene therapy</subject><subject>Gene Transfer Techniques</subject><subject>Graft Rejection - genetics</subject><subject>Graft Rejection - pathology</subject><subject>Graft Rejection - prevention & control</subject><subject>Graft Survival - genetics</subject><subject>interleukin-10</subject><subject>Interleukin-10 - biosynthesis</subject><subject>Interleukin-10 - genetics</subject><subject>lentiviral vector</subject><subject>limbal transplantation</subject><subject>Limbus Corneae - cytology</subject><subject>Limbus Corneae - surgery</subject><subject>Rats</subject><subject>Rats, Inbred F344</subject><subject>Rats, Inbred WF</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA - genetics</subject><subject>Transplantation, Homologous</subject><issn>0271-3683</issn><issn>1460-2202</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><recordid>eNp9kE1Lw0AQhhdRbK3-BCVHL6n7ncSTUrQWCoLU87KbzMJqsqm7CdJ_b0KqR08DL887MzwIXRO8JDjHd5hmhMmcLSkm2ZIwzjPCT9CccIlTSjE9RfORSUdohi5i_MB4DPg5mtG8oCJjdI7uN76DUEP_6XxKcLIGD8kuaB8thMT55E13ydY1RtdTvK-173TnWn-JzqyuI1wd5wK9Pz_tVi_p9nW9WT1u05JJ2aW0NIabIisNzaWQRgBnmSgAGyNyY4XWAFhyqMDqKgNd8ApbwCCJphqMZgt0O-3dh_arh9ipxsUS6uERaPuoSMGxKISgYkDFhJahjTGAVfvgGh0OimA1alO_2tSoTR21Db2b44neNFD9tX49DcDDBDhv29Do7zbUler0oW6DHbSULir2_40fHcV8MA</recordid><startdate>20171102</startdate><enddate>20171102</enddate><creator>Kaufmann, Claude</creator><creator>Mortimer, Lauren A</creator><creator>Brereton, Helen M</creator><creator>Irani, Yazad D</creator><creator>Parker, Douglas GA</creator><creator>Anson, Donald S</creator><creator>Bachmann, Lucas M</creator><creator>Williams, Keryn A</creator><general>Taylor & Francis</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></search><sort><creationdate>20171102</creationdate><title>Interleukin-10 Gene Transfer in Rat Limbal Transplantation</title><author>Kaufmann, Claude ; Mortimer, Lauren A ; Brereton, Helen M ; Irani, Yazad D ; Parker, Douglas GA ; Anson, Donald S ; Bachmann, Lucas M ; Williams, Keryn A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c366t-2cbb4b97cb28656b5e43759e0bb58bf5aaee064edefad7ea94d0fe0e61a2aeba3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adenoviral vector</topic><topic>Animals</topic><topic>Cells, Cultured</topic><topic>Corneal Diseases - pathology</topic><topic>Corneal Diseases - surgery</topic><topic>Corneal Transplantation - methods</topic><topic>Disease Models, Animal</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Follow-Up Studies</topic><topic>Gene Expression Regulation</topic><topic>gene therapy</topic><topic>Gene Transfer Techniques</topic><topic>Graft Rejection - genetics</topic><topic>Graft Rejection - pathology</topic><topic>Graft Rejection - prevention & control</topic><topic>Graft Survival - genetics</topic><topic>interleukin-10</topic><topic>Interleukin-10 - biosynthesis</topic><topic>Interleukin-10 - genetics</topic><topic>lentiviral vector</topic><topic>limbal transplantation</topic><topic>Limbus Corneae - cytology</topic><topic>Limbus Corneae - surgery</topic><topic>Rats</topic><topic>Rats, Inbred F344</topic><topic>Rats, Inbred WF</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA - genetics</topic><topic>Transplantation, Homologous</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kaufmann, Claude</creatorcontrib><creatorcontrib>Mortimer, Lauren A</creatorcontrib><creatorcontrib>Brereton, Helen M</creatorcontrib><creatorcontrib>Irani, Yazad D</creatorcontrib><creatorcontrib>Parker, Douglas GA</creatorcontrib><creatorcontrib>Anson, Donald S</creatorcontrib><creatorcontrib>Bachmann, Lucas M</creatorcontrib><creatorcontrib>Williams, Keryn A</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><jtitle>Current eye research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kaufmann, Claude</au><au>Mortimer, Lauren A</au><au>Brereton, Helen M</au><au>Irani, Yazad D</au><au>Parker, Douglas GA</au><au>Anson, Donald S</au><au>Bachmann, Lucas M</au><au>Williams, Keryn A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Interleukin-10 Gene Transfer in Rat Limbal Transplantation</atitle><jtitle>Current eye research</jtitle><addtitle>Curr Eye Res</addtitle><date>2017-11-02</date><risdate>2017</risdate><volume>42</volume><issue>11</issue><spage>1426</spage><epage>1434</epage><pages>1426-1434</pages><issn>0271-3683</issn><eissn>1460-2202</eissn><abstract>Purpose: To evaluate the gene transfer of the interleukin (IL)-10 cytokine as a treatment modality for prolonging limbal allograft survival in a rat model.
Materials and methods: Adenoviral (AV) and lentiviral (LV) vectors were produced for ex vivo gene transfer into limbal graft tissue prior to orthotopic transplantation. Experimental groups comprised unmodified isografts, unmodified allografts, allografts transfected with a reporter gene, and allografts transfected with IL-10. The functional effects of the transgenes were determined by clinical assessment and by following donor cell survival in the recipient animal. Group comparisons were made using survival analysis and tested with the log-rank test. Differences in mean rejection times between groups were tested using the Wilcoxon rank-sum test.
Results: Isografts survived during the entire observation period of 56 days. Allografts underwent clinical rejection at a mean of 6.7 days (standard deviation 2.0) postoperatively, irrespective of the presence of transgenes (p < 0.001 for difference in rejection times). For both the AV and LV vector systems, Kaplan-Meier analysis showed a statistically significant difference with respect to time-to-graft failure when comparing allografts transfected with IL-10 with allografts transfected with reporter gene alone (p = 0.011 and p < 0.001, respectively). In the isografts, donor cells could be detected during the complete observation period. In all the allograft groups, however, donor cell detection declined after 1 week and was lost after 4 weeks.
Conclusions: Under the conditions tested in the present model, both the AV and the LV vector systems were able to transfect limbal graft tissue ex vivo with biologically active IL-10, leading to delayed rejection compared to the controls.</abstract><cop>England</cop><pub>Taylor & Francis</pub><pmid>28925732</pmid><doi>10.1080/02713683.2017.1344714</doi><tpages>9</tpages></addata></record> |
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| ispartof | Current eye research, 2017-11, Vol.42 (11), p.1426-1434 |
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| language | eng |
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| source | Taylor and Francis:Jisc Collections:Taylor and Francis Read and Publish Agreement 2024-2025:Medical Collection (Reading list) |
| subjects | Adenoviral vector Animals Cells, Cultured Corneal Diseases - pathology Corneal Diseases - surgery Corneal Transplantation - methods Disease Models, Animal Enzyme-Linked Immunosorbent Assay Follow-Up Studies Gene Expression Regulation gene therapy Gene Transfer Techniques Graft Rejection - genetics Graft Rejection - pathology Graft Rejection - prevention & control Graft Survival - genetics interleukin-10 Interleukin-10 - biosynthesis Interleukin-10 - genetics lentiviral vector limbal transplantation Limbus Corneae - cytology Limbus Corneae - surgery Rats Rats, Inbred F344 Rats, Inbred WF Reverse Transcriptase Polymerase Chain Reaction RNA - genetics Transplantation, Homologous |
| title | Interleukin-10 Gene Transfer in Rat Limbal Transplantation |
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