In vivo use of oligonucleotides to inhibit choroidal neovascularisation in the eye
Background We have previously demonstrated the in vivo uptake of oligonucleotides in the rat eye and have continued with experiments to look at the effectiveness of targeted oligonucleotide sequences. Vascular endothelial growth factor (VEGF) is correlated with new blood vessel formation and has bee...
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| Veröffentlicht in: | The journal of gene medicine 2001-07, Vol.3 (4), p.373-383 |
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| creator | Garrett, Kerryn L. Shen, Wei-Yong Rakoczy, Piroska E. |
| description | Background
We have previously demonstrated the in vivo uptake of oligonucleotides in the rat eye and have continued with experiments to look at the effectiveness of targeted oligonucleotide sequences. Vascular endothelial growth factor (VEGF) is correlated with new blood vessel formation and has been implicated in numerous eye diseases characterised by abnormal blood vessel proliferation. An oligonucleotide targeted to the VEGF sequence was examined for its effect on VEGF production in vitro and the development of choroidal neovascularisation in vivo in the eye.
Methods
A series of sequences were assessed in an in vitro screening system using retinal pigment epithelial (RPE) cells to demonstrate a reduction in VEGF. A targeted sequence was further investigated using an animal model of choroidal neovascularisation where a krypton laser was used to produce a wound healing response in the choroid and retina. The oligonucleotide was injected into the vitreous and the development of choroidal neovascularisation assessed using fluorescein angiography.
Results
The targeted sequence was shown in vitro to downregulate the VEGF produced by RPE cells grown under hypoxic conditions and when injected into laser treated eyes was shown to be preferentially taken up in the laser lesion. Fluorescein angiography demonstrated that the test oligonucleotide was successful in reducing laser‐mediated choroidal neovascularisation.
Conclusions
A sequence corresponding to the 5′UTR of the VEGF gene has provided encouraging results for the treatment of neovascularisation. Copyright © 2001 John Wiley & Sons, Ltd. |
| doi_str_mv | 10.1002/jgm.197 |
| format | Article |
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We have previously demonstrated the in vivo uptake of oligonucleotides in the rat eye and have continued with experiments to look at the effectiveness of targeted oligonucleotide sequences. Vascular endothelial growth factor (VEGF) is correlated with new blood vessel formation and has been implicated in numerous eye diseases characterised by abnormal blood vessel proliferation. An oligonucleotide targeted to the VEGF sequence was examined for its effect on VEGF production in vitro and the development of choroidal neovascularisation in vivo in the eye.
Methods
A series of sequences were assessed in an in vitro screening system using retinal pigment epithelial (RPE) cells to demonstrate a reduction in VEGF. A targeted sequence was further investigated using an animal model of choroidal neovascularisation where a krypton laser was used to produce a wound healing response in the choroid and retina. The oligonucleotide was injected into the vitreous and the development of choroidal neovascularisation assessed using fluorescein angiography.
Results
The targeted sequence was shown in vitro to downregulate the VEGF produced by RPE cells grown under hypoxic conditions and when injected into laser treated eyes was shown to be preferentially taken up in the laser lesion. Fluorescein angiography demonstrated that the test oligonucleotide was successful in reducing laser‐mediated choroidal neovascularisation.
Conclusions
A sequence corresponding to the 5′UTR of the VEGF gene has provided encouraging results for the treatment of neovascularisation. Copyright © 2001 John Wiley & Sons, Ltd.</description><identifier>ISSN: 1099-498X</identifier><identifier>EISSN: 1521-2254</identifier><identifier>DOI: 10.1002/jgm.197</identifier><identifier>PMID: 11529667</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>Animals ; Base Sequence ; Choroid - blood supply ; choroidal neovascularisation ; Endothelial Growth Factors - antagonists & inhibitors ; Endothelial Growth Factors - genetics ; eye ; Gene therapy ; Laser Coagulation ; Lymphokines - antagonists & inhibitors ; Lymphokines - genetics ; Neovascularization, Pathologic - prevention & control ; Oligodeoxyribonucleotides, Antisense - chemistry ; Oligodeoxyribonucleotides, Antisense - pharmacokinetics ; Oligodeoxyribonucleotides, Antisense - therapeutic use ; oligonucleotides ; Pigment Epithelium of Eye - blood supply ; Rats ; retinal pigment epithelial cells ; Reverse Transcriptase Polymerase Chain Reaction ; Structure-Activity Relationship ; Tissue Distribution ; vascular endothelial growth factor ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors ; VEGF</subject><ispartof>The journal of gene medicine, 2001-07, Vol.3 (4), p.373-383</ispartof><rights>Copyright © 2001 John Wiley & Sons, Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4097-90d7582839e51ae18b93aaf0a3bf18688e77c8b73c8e5867d2eb24c24211eba3</citedby><cites>FETCH-LOGICAL-c4097-90d7582839e51ae18b93aaf0a3bf18688e77c8b73c8e5867d2eb24c24211eba3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjgm.197$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjgm.197$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11529667$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Garrett, Kerryn L.</creatorcontrib><creatorcontrib>Shen, Wei-Yong</creatorcontrib><creatorcontrib>Rakoczy, Piroska E.</creatorcontrib><title>In vivo use of oligonucleotides to inhibit choroidal neovascularisation in the eye</title><title>The journal of gene medicine</title><addtitle>J. Gene Med</addtitle><description>Background
We have previously demonstrated the in vivo uptake of oligonucleotides in the rat eye and have continued with experiments to look at the effectiveness of targeted oligonucleotide sequences. Vascular endothelial growth factor (VEGF) is correlated with new blood vessel formation and has been implicated in numerous eye diseases characterised by abnormal blood vessel proliferation. An oligonucleotide targeted to the VEGF sequence was examined for its effect on VEGF production in vitro and the development of choroidal neovascularisation in vivo in the eye.
Methods
A series of sequences were assessed in an in vitro screening system using retinal pigment epithelial (RPE) cells to demonstrate a reduction in VEGF. A targeted sequence was further investigated using an animal model of choroidal neovascularisation where a krypton laser was used to produce a wound healing response in the choroid and retina. The oligonucleotide was injected into the vitreous and the development of choroidal neovascularisation assessed using fluorescein angiography.
Results
The targeted sequence was shown in vitro to downregulate the VEGF produced by RPE cells grown under hypoxic conditions and when injected into laser treated eyes was shown to be preferentially taken up in the laser lesion. Fluorescein angiography demonstrated that the test oligonucleotide was successful in reducing laser‐mediated choroidal neovascularisation.
Conclusions
A sequence corresponding to the 5′UTR of the VEGF gene has provided encouraging results for the treatment of neovascularisation. Copyright © 2001 John Wiley & Sons, Ltd.</description><subject>Animals</subject><subject>Base Sequence</subject><subject>Choroid - blood supply</subject><subject>choroidal neovascularisation</subject><subject>Endothelial Growth Factors - antagonists & inhibitors</subject><subject>Endothelial Growth Factors - genetics</subject><subject>eye</subject><subject>Gene therapy</subject><subject>Laser Coagulation</subject><subject>Lymphokines - antagonists & inhibitors</subject><subject>Lymphokines - genetics</subject><subject>Neovascularization, Pathologic - prevention & control</subject><subject>Oligodeoxyribonucleotides, Antisense - chemistry</subject><subject>Oligodeoxyribonucleotides, Antisense - pharmacokinetics</subject><subject>Oligodeoxyribonucleotides, Antisense - therapeutic use</subject><subject>oligonucleotides</subject><subject>Pigment Epithelium of Eye - blood supply</subject><subject>Rats</subject><subject>retinal pigment epithelial cells</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Structure-Activity Relationship</subject><subject>Tissue Distribution</subject><subject>vascular endothelial growth factor</subject><subject>Vascular Endothelial Growth Factor A</subject><subject>Vascular Endothelial Growth Factors</subject><subject>VEGF</subject><issn>1099-498X</issn><issn>1521-2254</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqF0d9rFDEQB_Agiq1V_A8k-KAPsjWT_ZHJoxR7VloVKdi3kM3O9nLubWqye3r_vZE9FAQRAjMPH75MZhh7CuIUhJCvN7fbU9DqHjuGWkIhZV3dz73Quqg03hyxRylthACFqB-yI8hKN406Zp8vRr7zu8DnRDz0PAz-NoyzGyhMvqPEp8D9uPatn7hbhxh8Zwc-UtjZ5ObBRp_s5MOYEZ_WxGlPj9mD3g6JnhzqCbs-f3t99q64_Li6OHtzWbhKaFVo0akaJZaaarAE2OrS2l7Ysu0BG0RSymGrSodUY6M6Sa2snKwkALW2PGEvlti7GL7NlCaz9cnRMNg83ZyMApC6zO9_EFBoIRAzfP4X3IQ5jvkPBnSjAaUWGb1ckIshpUi9uYt-a-PegDC_bmHyLbJXWT47xM3tlro_7rD8DF4t4LsfaP-vHPN-dbXEFYv2aaIfv7WNX03OUrX58mFlbvDTeXOlc1P-BHfhoO8</recordid><startdate>200107</startdate><enddate>200107</enddate><creator>Garrett, Kerryn L.</creator><creator>Shen, Wei-Yong</creator><creator>Rakoczy, Piroska E.</creator><general>John Wiley & Sons, Ltd</general><general>Wiley Periodicals Inc</general><scope>BSCLL</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>3V.</scope><scope>7QP</scope><scope>7TK</scope><scope>7TM</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7QO</scope><scope>7X8</scope></search><sort><creationdate>200107</creationdate><title>In vivo use of oligonucleotides to inhibit choroidal neovascularisation in the eye</title><author>Garrett, Kerryn L. ; Shen, Wei-Yong ; Rakoczy, Piroska E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4097-90d7582839e51ae18b93aaf0a3bf18688e77c8b73c8e5867d2eb24c24211eba3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Animals</topic><topic>Base Sequence</topic><topic>Choroid - blood supply</topic><topic>choroidal neovascularisation</topic><topic>Endothelial Growth Factors - antagonists & inhibitors</topic><topic>Endothelial Growth Factors - genetics</topic><topic>eye</topic><topic>Gene therapy</topic><topic>Laser Coagulation</topic><topic>Lymphokines - antagonists & inhibitors</topic><topic>Lymphokines - genetics</topic><topic>Neovascularization, Pathologic - prevention & control</topic><topic>Oligodeoxyribonucleotides, Antisense - chemistry</topic><topic>Oligodeoxyribonucleotides, Antisense - pharmacokinetics</topic><topic>Oligodeoxyribonucleotides, Antisense - therapeutic use</topic><topic>oligonucleotides</topic><topic>Pigment Epithelium of Eye - blood supply</topic><topic>Rats</topic><topic>retinal pigment epithelial cells</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Structure-Activity Relationship</topic><topic>Tissue Distribution</topic><topic>vascular endothelial growth factor</topic><topic>Vascular Endothelial Growth Factor A</topic><topic>Vascular Endothelial Growth Factors</topic><topic>VEGF</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Garrett, Kerryn L.</creatorcontrib><creatorcontrib>Shen, Wei-Yong</creatorcontrib><creatorcontrib>Rakoczy, Piroska E.</creatorcontrib><collection>Istex</collection><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>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</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)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biological Sciences</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</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>Genetics Abstracts</collection><collection>Biotechnology Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The journal of gene medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Garrett, Kerryn L.</au><au>Shen, Wei-Yong</au><au>Rakoczy, Piroska E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>In vivo use of oligonucleotides to inhibit choroidal neovascularisation in the eye</atitle><jtitle>The journal of gene medicine</jtitle><addtitle>J. Gene Med</addtitle><date>2001-07</date><risdate>2001</risdate><volume>3</volume><issue>4</issue><spage>373</spage><epage>383</epage><pages>373-383</pages><issn>1099-498X</issn><eissn>1521-2254</eissn><abstract>Background
We have previously demonstrated the in vivo uptake of oligonucleotides in the rat eye and have continued with experiments to look at the effectiveness of targeted oligonucleotide sequences. Vascular endothelial growth factor (VEGF) is correlated with new blood vessel formation and has been implicated in numerous eye diseases characterised by abnormal blood vessel proliferation. An oligonucleotide targeted to the VEGF sequence was examined for its effect on VEGF production in vitro and the development of choroidal neovascularisation in vivo in the eye.
Methods
A series of sequences were assessed in an in vitro screening system using retinal pigment epithelial (RPE) cells to demonstrate a reduction in VEGF. A targeted sequence was further investigated using an animal model of choroidal neovascularisation where a krypton laser was used to produce a wound healing response in the choroid and retina. The oligonucleotide was injected into the vitreous and the development of choroidal neovascularisation assessed using fluorescein angiography.
Results
The targeted sequence was shown in vitro to downregulate the VEGF produced by RPE cells grown under hypoxic conditions and when injected into laser treated eyes was shown to be preferentially taken up in the laser lesion. Fluorescein angiography demonstrated that the test oligonucleotide was successful in reducing laser‐mediated choroidal neovascularisation.
Conclusions
A sequence corresponding to the 5′UTR of the VEGF gene has provided encouraging results for the treatment of neovascularisation. Copyright © 2001 John Wiley & Sons, Ltd.</abstract><cop>Chichester, UK</cop><pub>John Wiley & Sons, Ltd</pub><pmid>11529667</pmid><doi>10.1002/jgm.197</doi><tpages>11</tpages></addata></record> |
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| source | MEDLINE; Wiley Online Library Journals |
| subjects | Animals Base Sequence Choroid - blood supply choroidal neovascularisation Endothelial Growth Factors - antagonists & inhibitors Endothelial Growth Factors - genetics eye Gene therapy Laser Coagulation Lymphokines - antagonists & inhibitors Lymphokines - genetics Neovascularization, Pathologic - prevention & control Oligodeoxyribonucleotides, Antisense - chemistry Oligodeoxyribonucleotides, Antisense - pharmacokinetics Oligodeoxyribonucleotides, Antisense - therapeutic use oligonucleotides Pigment Epithelium of Eye - blood supply Rats retinal pigment epithelial cells Reverse Transcriptase Polymerase Chain Reaction Structure-Activity Relationship Tissue Distribution vascular endothelial growth factor Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors VEGF |
| title | In vivo use of oligonucleotides to inhibit choroidal neovascularisation in the eye |
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