Intravitreal itraconazole inhibits laser-induced choroidal neovascularization in rats
Choroidal neovascularization (CNV) is a major cause of severe visual loss in patients with age-related macular degeneration (AMD). Recently, itraconazole has shown potent and dose-dependent inhibition of tumor-associated angiogenesis. We evaluated the anti-angiogenic effect of itraconazole in a rat...
Gespeichert in:
| Veröffentlicht in: | PloS one 2017-06, Vol.12 (6), p.e0180482-e0180482 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | e0180482 |
|---|---|
| container_issue | 6 |
| container_start_page | e0180482 |
| container_title | PloS one |
| container_volume | 12 |
| creator | Bae, Jeong Hun Hwang, Ah Reum Kim, Chan Yun Yu, Hyeong Gon Koh, Hyoung Jun Yang, Woo Ick Chang, Hae Ran Lee, Sung Chul |
| description | Choroidal neovascularization (CNV) is a major cause of severe visual loss in patients with age-related macular degeneration (AMD). Recently, itraconazole has shown potent and dose-dependent inhibition of tumor-associated angiogenesis. We evaluated the anti-angiogenic effect of itraconazole in a rat model of laser-induced CNV. After laser photocoagulation in each eye to cause CNV, right eyes were administered intravitreal injections of itraconazole; left eyes received balanced salt solution (BSS) as controls. On day 14 after laser induction, fluorescein angiography (FA) was used to assess abnormal vascular leakage. Flattened retinal pigment epithelium (RPE)-choroid tissue complex was stained with Alexa Fluor 594-conjugated isolectin B4 to measure the CNV area and volume. Vascular endothelial growth factor receptor 2 (VEGFR2) mRNA and protein expression was determined 1, 4, 7, and 14 days after intravitreal injection by quantitative RT-PCR or Western blot. VEGF levels were analyzed by enzyme-linked immunosorbent assay (ELISA). Intravitreal itraconazole significantly reduced leakage from CNV as assessed by FA and CNV area and volume on flat mounts compared with intravitreal BSS (p = 0.002 for CNV leakage, p |
| doi_str_mv | 10.1371/journal.pone.0180482 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1914988492</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A497491304</galeid><doaj_id>oai_doaj_org_article_06c5fb3841624c97a8756ec6094786a3</doaj_id><sourcerecordid>A497491304</sourcerecordid><originalsourceid>FETCH-LOGICAL-c758t-d38b0508670a292f24471f706feb9f0ac02c9dbd8b235bcd14b20cbd4cf78f433</originalsourceid><addsrcrecordid>eNqNkl1rFDEUhgdRbK3-A9EFQfRi13xNJrkRSvFjoVBQ623I5GM3S3ayJplF--vNdKdlR3ohc3GG5Dlvkve8VfUSggXEDfywCX3spF_sQmcWADJAGHpUnUKO0ZwigB8f_Z9Uz1LaAFBjRunT6gSVQgFCp9X1sstR7l2ORvpZKVKFTt4Eb2auW7vW5TTzMpk4d53uldEztQ4xOF3ozoS9TKr3MrobmV3oSs8sypyeV0-s9Mm8GOtZdf3504-Lr_PLqy_Li_PLuWpqlucasxbUgNEGSMSRRYQ00DaAWtNyC6QCSHHdatYiXLdKQ9IioFpNlG2YJRifVa8PujsfkhgdSQJySDhjhKNCLA-EDnIjdtFtZfwjgnTidiHElZAxO-WNAFTVtsWMQIqI4o1kTU2NooCThlE5nPZxPK1vt0YrM1jnJ6LTnc6txSrsRU04JoAWgXejQAy_epOy2LqkjPeyWNnf3rvGhNeQFPTNP-jDrxuplSwPcJ0NwwAHUXFOeEM4xGDQWjxAlU-brSvjNtaV9UnD-0lDYbL5nVeyT0ksv3_7f_bq55R9e8SuS-LyOgXfD9FJU5AcQBVDStHYe5MhEEP679wQQ_rFmP7S9up4QPdNd3HHfwGv1QAG</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1914988492</pqid></control><display><type>article</type><title>Intravitreal itraconazole inhibits laser-induced choroidal neovascularization in rats</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Public Library of Science (PLoS) Journals Open Access</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Bae, Jeong Hun ; Hwang, Ah Reum ; Kim, Chan Yun ; Yu, Hyeong Gon ; Koh, Hyoung Jun ; Yang, Woo Ick ; Chang, Hae Ran ; Lee, Sung Chul</creator><contributor>Lewin, Alfred S.</contributor><creatorcontrib>Bae, Jeong Hun ; Hwang, Ah Reum ; Kim, Chan Yun ; Yu, Hyeong Gon ; Koh, Hyoung Jun ; Yang, Woo Ick ; Chang, Hae Ran ; Lee, Sung Chul ; Lewin, Alfred S.</creatorcontrib><description>Choroidal neovascularization (CNV) is a major cause of severe visual loss in patients with age-related macular degeneration (AMD). Recently, itraconazole has shown potent and dose-dependent inhibition of tumor-associated angiogenesis. We evaluated the anti-angiogenic effect of itraconazole in a rat model of laser-induced CNV. After laser photocoagulation in each eye to cause CNV, right eyes were administered intravitreal injections of itraconazole; left eyes received balanced salt solution (BSS) as controls. On day 14 after laser induction, fluorescein angiography (FA) was used to assess abnormal vascular leakage. Flattened retinal pigment epithelium (RPE)-choroid tissue complex was stained with Alexa Fluor 594-conjugated isolectin B4 to measure the CNV area and volume. Vascular endothelial growth factor receptor 2 (VEGFR2) mRNA and protein expression was determined 1, 4, 7, and 14 days after intravitreal injection by quantitative RT-PCR or Western blot. VEGF levels were analyzed by enzyme-linked immunosorbent assay (ELISA). Intravitreal itraconazole significantly reduced leakage from CNV as assessed by FA and CNV area and volume on flat mounts compared with intravitreal BSS (p = 0.002 for CNV leakage, p<0.001 for CNV area and volume). Quantitative RT-PCR showed significantly lower expression of VEGFR2 mRNA in the RPE-choroid complexes of itraconazole-injected eyes than those of BSS-injected eyes on days 7 and 14 (p = 0.003 and p = 0.006). Western blots indicated that VEGFR2 was downregulated after itraconazole treatment. ELISA showed a significant difference in VEGF level between itraconazole-injected and BSS-injected eyes on days 7 and 14 (p = 0.04 and p = 0.001). Our study demonstrated that intravitreal itraconazole significantly inhibited the development of laser-induced CNV in rats. Itraconazole had anti-angiogenic activity along with the reduction of VEGFR2 and VEGF levels. Itraconazole may prove beneficial for treating CNV as an alternative or adjunct to other therapies.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0180482</identifier><identifier>PMID: 28666022</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Age ; Angiogenesis ; Angiography ; Animals ; Antifungal agents ; Biology and Life Sciences ; Care and treatment ; Cell growth ; Choroidal Neovascularization - etiology ; Choroidal Neovascularization - prevention & control ; Dosage and administration ; Drug therapy ; Engineering and Technology ; Enzyme-Linked Immunosorbent Assay ; Epithelium ; Eye ; Eye (anatomy) ; Flattening ; Fluorescein ; Fluorescein Angiography ; Gene expression ; Intravitreal Injections ; Itraconazole ; Itraconazole - administration & dosage ; Itraconazole - therapeutic use ; Kinases ; Laser Coagulation - adverse effects ; Lasers ; Leakage ; Macular degeneration ; Male ; Medicine and Health Sciences ; mRNA ; Neovascularization ; Physicians ; Polymerase chain reaction ; Rats ; Real-Time Polymerase Chain Reaction ; Research and Analysis Methods ; Retina ; Retinal pigment epithelium ; Rodents ; Salts ; Vascular endothelial growth factor ; Vascular Endothelial Growth Factor A - metabolism ; Vascular endothelial growth factor receptor 2 ; Vascular Endothelial Growth Factor Receptor-2 - genetics ; Vascular Endothelial Growth Factor Receptor-2 - metabolism ; Vascularization ; Visual perception ; Western blotting</subject><ispartof>PloS one, 2017-06, Vol.12 (6), p.e0180482-e0180482</ispartof><rights>COPYRIGHT 2017 Public Library of Science</rights><rights>2017 Bae et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2017 Bae et al 2017 Bae et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-d38b0508670a292f24471f706feb9f0ac02c9dbd8b235bcd14b20cbd4cf78f433</citedby><cites>FETCH-LOGICAL-c758t-d38b0508670a292f24471f706feb9f0ac02c9dbd8b235bcd14b20cbd4cf78f433</cites><orcidid>0000-0001-9438-2385</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5493406/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5493406/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28666022$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Lewin, Alfred S.</contributor><creatorcontrib>Bae, Jeong Hun</creatorcontrib><creatorcontrib>Hwang, Ah Reum</creatorcontrib><creatorcontrib>Kim, Chan Yun</creatorcontrib><creatorcontrib>Yu, Hyeong Gon</creatorcontrib><creatorcontrib>Koh, Hyoung Jun</creatorcontrib><creatorcontrib>Yang, Woo Ick</creatorcontrib><creatorcontrib>Chang, Hae Ran</creatorcontrib><creatorcontrib>Lee, Sung Chul</creatorcontrib><title>Intravitreal itraconazole inhibits laser-induced choroidal neovascularization in rats</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Choroidal neovascularization (CNV) is a major cause of severe visual loss in patients with age-related macular degeneration (AMD). Recently, itraconazole has shown potent and dose-dependent inhibition of tumor-associated angiogenesis. We evaluated the anti-angiogenic effect of itraconazole in a rat model of laser-induced CNV. After laser photocoagulation in each eye to cause CNV, right eyes were administered intravitreal injections of itraconazole; left eyes received balanced salt solution (BSS) as controls. On day 14 after laser induction, fluorescein angiography (FA) was used to assess abnormal vascular leakage. Flattened retinal pigment epithelium (RPE)-choroid tissue complex was stained with Alexa Fluor 594-conjugated isolectin B4 to measure the CNV area and volume. Vascular endothelial growth factor receptor 2 (VEGFR2) mRNA and protein expression was determined 1, 4, 7, and 14 days after intravitreal injection by quantitative RT-PCR or Western blot. VEGF levels were analyzed by enzyme-linked immunosorbent assay (ELISA). Intravitreal itraconazole significantly reduced leakage from CNV as assessed by FA and CNV area and volume on flat mounts compared with intravitreal BSS (p = 0.002 for CNV leakage, p<0.001 for CNV area and volume). Quantitative RT-PCR showed significantly lower expression of VEGFR2 mRNA in the RPE-choroid complexes of itraconazole-injected eyes than those of BSS-injected eyes on days 7 and 14 (p = 0.003 and p = 0.006). Western blots indicated that VEGFR2 was downregulated after itraconazole treatment. ELISA showed a significant difference in VEGF level between itraconazole-injected and BSS-injected eyes on days 7 and 14 (p = 0.04 and p = 0.001). Our study demonstrated that intravitreal itraconazole significantly inhibited the development of laser-induced CNV in rats. Itraconazole had anti-angiogenic activity along with the reduction of VEGFR2 and VEGF levels. Itraconazole may prove beneficial for treating CNV as an alternative or adjunct to other therapies.</description><subject>Age</subject><subject>Angiogenesis</subject><subject>Angiography</subject><subject>Animals</subject><subject>Antifungal agents</subject><subject>Biology and Life Sciences</subject><subject>Care and treatment</subject><subject>Cell growth</subject><subject>Choroidal Neovascularization - etiology</subject><subject>Choroidal Neovascularization - prevention & control</subject><subject>Dosage and administration</subject><subject>Drug therapy</subject><subject>Engineering and Technology</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Epithelium</subject><subject>Eye</subject><subject>Eye (anatomy)</subject><subject>Flattening</subject><subject>Fluorescein</subject><subject>Fluorescein Angiography</subject><subject>Gene expression</subject><subject>Intravitreal Injections</subject><subject>Itraconazole</subject><subject>Itraconazole - administration & dosage</subject><subject>Itraconazole - therapeutic use</subject><subject>Kinases</subject><subject>Laser Coagulation - adverse effects</subject><subject>Lasers</subject><subject>Leakage</subject><subject>Macular degeneration</subject><subject>Male</subject><subject>Medicine and Health Sciences</subject><subject>mRNA</subject><subject>Neovascularization</subject><subject>Physicians</subject><subject>Polymerase chain reaction</subject><subject>Rats</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Research and Analysis Methods</subject><subject>Retina</subject><subject>Retinal pigment epithelium</subject><subject>Rodents</subject><subject>Salts</subject><subject>Vascular endothelial growth factor</subject><subject>Vascular Endothelial Growth Factor A - metabolism</subject><subject>Vascular endothelial growth factor receptor 2</subject><subject>Vascular Endothelial Growth Factor Receptor-2 - genetics</subject><subject>Vascular Endothelial Growth Factor Receptor-2 - metabolism</subject><subject>Vascularization</subject><subject>Visual perception</subject><subject>Western blotting</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNkl1rFDEUhgdRbK3-A9EFQfRi13xNJrkRSvFjoVBQ623I5GM3S3ayJplF--vNdKdlR3ohc3GG5Dlvkve8VfUSggXEDfywCX3spF_sQmcWADJAGHpUnUKO0ZwigB8f_Z9Uz1LaAFBjRunT6gSVQgFCp9X1sstR7l2ORvpZKVKFTt4Eb2auW7vW5TTzMpk4d53uldEztQ4xOF3ozoS9TKr3MrobmV3oSs8sypyeV0-s9Mm8GOtZdf3504-Lr_PLqy_Li_PLuWpqlucasxbUgNEGSMSRRYQ00DaAWtNyC6QCSHHdatYiXLdKQ9IioFpNlG2YJRifVa8PujsfkhgdSQJySDhjhKNCLA-EDnIjdtFtZfwjgnTidiHElZAxO-WNAFTVtsWMQIqI4o1kTU2NooCThlE5nPZxPK1vt0YrM1jnJ6LTnc6txSrsRU04JoAWgXejQAy_epOy2LqkjPeyWNnf3rvGhNeQFPTNP-jDrxuplSwPcJ0NwwAHUXFOeEM4xGDQWjxAlU-brSvjNtaV9UnD-0lDYbL5nVeyT0ksv3_7f_bq55R9e8SuS-LyOgXfD9FJU5AcQBVDStHYe5MhEEP679wQQ_rFmP7S9up4QPdNd3HHfwGv1QAG</recordid><startdate>20170630</startdate><enddate>20170630</enddate><creator>Bae, Jeong Hun</creator><creator>Hwang, Ah Reum</creator><creator>Kim, Chan Yun</creator><creator>Yu, Hyeong Gon</creator><creator>Koh, Hyoung Jun</creator><creator>Yang, Woo Ick</creator><creator>Chang, Hae Ran</creator><creator>Lee, Sung Chul</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0001-9438-2385</orcidid></search><sort><creationdate>20170630</creationdate><title>Intravitreal itraconazole inhibits laser-induced choroidal neovascularization in rats</title><author>Bae, Jeong Hun ; Hwang, Ah Reum ; Kim, Chan Yun ; Yu, Hyeong Gon ; Koh, Hyoung Jun ; Yang, Woo Ick ; Chang, Hae Ran ; Lee, Sung Chul</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-d38b0508670a292f24471f706feb9f0ac02c9dbd8b235bcd14b20cbd4cf78f433</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Age</topic><topic>Angiogenesis</topic><topic>Angiography</topic><topic>Animals</topic><topic>Antifungal agents</topic><topic>Biology and Life Sciences</topic><topic>Care and treatment</topic><topic>Cell growth</topic><topic>Choroidal Neovascularization - etiology</topic><topic>Choroidal Neovascularization - prevention & control</topic><topic>Dosage and administration</topic><topic>Drug therapy</topic><topic>Engineering and Technology</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Epithelium</topic><topic>Eye</topic><topic>Eye (anatomy)</topic><topic>Flattening</topic><topic>Fluorescein</topic><topic>Fluorescein Angiography</topic><topic>Gene expression</topic><topic>Intravitreal Injections</topic><topic>Itraconazole</topic><topic>Itraconazole - administration & dosage</topic><topic>Itraconazole - therapeutic use</topic><topic>Kinases</topic><topic>Laser Coagulation - adverse effects</topic><topic>Lasers</topic><topic>Leakage</topic><topic>Macular degeneration</topic><topic>Male</topic><topic>Medicine and Health Sciences</topic><topic>mRNA</topic><topic>Neovascularization</topic><topic>Physicians</topic><topic>Polymerase chain reaction</topic><topic>Rats</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Research and Analysis Methods</topic><topic>Retina</topic><topic>Retinal pigment epithelium</topic><topic>Rodents</topic><topic>Salts</topic><topic>Vascular endothelial growth factor</topic><topic>Vascular Endothelial Growth Factor A - metabolism</topic><topic>Vascular endothelial growth factor receptor 2</topic><topic>Vascular Endothelial Growth Factor Receptor-2 - genetics</topic><topic>Vascular Endothelial Growth Factor Receptor-2 - metabolism</topic><topic>Vascularization</topic><topic>Visual perception</topic><topic>Western blotting</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bae, Jeong Hun</creatorcontrib><creatorcontrib>Hwang, Ah Reum</creatorcontrib><creatorcontrib>Kim, Chan Yun</creatorcontrib><creatorcontrib>Yu, Hyeong Gon</creatorcontrib><creatorcontrib>Koh, Hyoung Jun</creatorcontrib><creatorcontrib>Yang, Woo Ick</creatorcontrib><creatorcontrib>Chang, Hae Ran</creatorcontrib><creatorcontrib>Lee, Sung Chul</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology 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>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</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>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content 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>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bae, Jeong Hun</au><au>Hwang, Ah Reum</au><au>Kim, Chan Yun</au><au>Yu, Hyeong Gon</au><au>Koh, Hyoung Jun</au><au>Yang, Woo Ick</au><au>Chang, Hae Ran</au><au>Lee, Sung Chul</au><au>Lewin, Alfred S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Intravitreal itraconazole inhibits laser-induced choroidal neovascularization in rats</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2017-06-30</date><risdate>2017</risdate><volume>12</volume><issue>6</issue><spage>e0180482</spage><epage>e0180482</epage><pages>e0180482-e0180482</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Choroidal neovascularization (CNV) is a major cause of severe visual loss in patients with age-related macular degeneration (AMD). Recently, itraconazole has shown potent and dose-dependent inhibition of tumor-associated angiogenesis. We evaluated the anti-angiogenic effect of itraconazole in a rat model of laser-induced CNV. After laser photocoagulation in each eye to cause CNV, right eyes were administered intravitreal injections of itraconazole; left eyes received balanced salt solution (BSS) as controls. On day 14 after laser induction, fluorescein angiography (FA) was used to assess abnormal vascular leakage. Flattened retinal pigment epithelium (RPE)-choroid tissue complex was stained with Alexa Fluor 594-conjugated isolectin B4 to measure the CNV area and volume. Vascular endothelial growth factor receptor 2 (VEGFR2) mRNA and protein expression was determined 1, 4, 7, and 14 days after intravitreal injection by quantitative RT-PCR or Western blot. VEGF levels were analyzed by enzyme-linked immunosorbent assay (ELISA). Intravitreal itraconazole significantly reduced leakage from CNV as assessed by FA and CNV area and volume on flat mounts compared with intravitreal BSS (p = 0.002 for CNV leakage, p<0.001 for CNV area and volume). Quantitative RT-PCR showed significantly lower expression of VEGFR2 mRNA in the RPE-choroid complexes of itraconazole-injected eyes than those of BSS-injected eyes on days 7 and 14 (p = 0.003 and p = 0.006). Western blots indicated that VEGFR2 was downregulated after itraconazole treatment. ELISA showed a significant difference in VEGF level between itraconazole-injected and BSS-injected eyes on days 7 and 14 (p = 0.04 and p = 0.001). Our study demonstrated that intravitreal itraconazole significantly inhibited the development of laser-induced CNV in rats. Itraconazole had anti-angiogenic activity along with the reduction of VEGFR2 and VEGF levels. Itraconazole may prove beneficial for treating CNV as an alternative or adjunct to other therapies.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>28666022</pmid><doi>10.1371/journal.pone.0180482</doi><tpages>e0180482</tpages><orcidid>https://orcid.org/0000-0001-9438-2385</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2017-06, Vol.12 (6), p.e0180482-e0180482 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1914988492 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Age Angiogenesis Angiography Animals Antifungal agents Biology and Life Sciences Care and treatment Cell growth Choroidal Neovascularization - etiology Choroidal Neovascularization - prevention & control Dosage and administration Drug therapy Engineering and Technology Enzyme-Linked Immunosorbent Assay Epithelium Eye Eye (anatomy) Flattening Fluorescein Fluorescein Angiography Gene expression Intravitreal Injections Itraconazole Itraconazole - administration & dosage Itraconazole - therapeutic use Kinases Laser Coagulation - adverse effects Lasers Leakage Macular degeneration Male Medicine and Health Sciences mRNA Neovascularization Physicians Polymerase chain reaction Rats Real-Time Polymerase Chain Reaction Research and Analysis Methods Retina Retinal pigment epithelium Rodents Salts Vascular endothelial growth factor Vascular Endothelial Growth Factor A - metabolism Vascular endothelial growth factor receptor 2 Vascular Endothelial Growth Factor Receptor-2 - genetics Vascular Endothelial Growth Factor Receptor-2 - metabolism Vascularization Visual perception Western blotting |
| title | Intravitreal itraconazole inhibits laser-induced choroidal neovascularization in rats |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-26T10%3A27%3A46IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Intravitreal%20itraconazole%20inhibits%20laser-induced%20choroidal%20neovascularization%20in%20rats&rft.jtitle=PloS%20one&rft.au=Bae,%20Jeong%20Hun&rft.date=2017-06-30&rft.volume=12&rft.issue=6&rft.spage=e0180482&rft.epage=e0180482&rft.pages=e0180482-e0180482&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0180482&rft_dat=%3Cgale_plos_%3EA497491304%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1914988492&rft_id=info:pmid/28666022&rft_galeid=A497491304&rft_doaj_id=oai_doaj_org_article_06c5fb3841624c97a8756ec6094786a3&rfr_iscdi=true |