Antiangiogenic Effects of Doxazosin on Experimental Choroidal Neovascularization in Mice
The present study was designed to evaluate the effects of doxazosin on experimental choroidal neovascularization (CNV) in mice. Six- to 8-week-old male C57BL/6 mice were divided into a control group and a doxazosin-treated group (5 mg/kg, i.p., daily). Experimental CNV was induced by laser photocoag...
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| Veröffentlicht in: | Journal of ocular pharmacology and therapeutics 2017-01, Vol.33 (1), p.50-56 |
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| creator | Guo, Jiaxian Luo, Xueting Liang, Jian Xiao, Meichun Sun, Xiaodong |
| description | The present study was designed to evaluate the effects of doxazosin on experimental choroidal neovascularization (CNV) in mice.
Six- to 8-week-old male C57BL/6 mice were divided into a control group and a doxazosin-treated group (5 mg/kg, i.p., daily). Experimental CNV was induced by laser photocoagulation. Seven and 14 days after laser induction, fluorescein angiography, choroidal flat mounts, and histological studies were performed to evaluate the fluorescence leakage, area, and thickness of CNV lesions, respectively. In addition, western blot analysis was carried out to assess the inhibitory effects of doxazosin on the PI3K/Akt/mTOR signaling pathway and the expression levels of hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF), which are involved in CNV model.
Compared with the control group, the doxazosin-treated group demonstrated significantly less fluorescence leakage on day 7 and 14 after laser induction. Both the area and the thickness of CNV lesions in the doxazosin-treated group were significantly decreased. Mechanistically, PI3K/Akt/mTOR signaling pathway activation was significantly suppressed in the doxazosin-treated group. The expression of HIF-1α and VEGF was also notably reduced by systemic doxazosin treatment.
Doxazosin exerts antiangiogenic actions in an experimental mouse model of CNV and may be a potential adjunctive therapy for neovascular age-related macular degeneration in humans. |
| doi_str_mv | 10.1089/jop.2016.0153 |
| format | Article |
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Six- to 8-week-old male C57BL/6 mice were divided into a control group and a doxazosin-treated group (5 mg/kg, i.p., daily). Experimental CNV was induced by laser photocoagulation. Seven and 14 days after laser induction, fluorescein angiography, choroidal flat mounts, and histological studies were performed to evaluate the fluorescence leakage, area, and thickness of CNV lesions, respectively. In addition, western blot analysis was carried out to assess the inhibitory effects of doxazosin on the PI3K/Akt/mTOR signaling pathway and the expression levels of hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF), which are involved in CNV model.
Compared with the control group, the doxazosin-treated group demonstrated significantly less fluorescence leakage on day 7 and 14 after laser induction. Both the area and the thickness of CNV lesions in the doxazosin-treated group were significantly decreased. Mechanistically, PI3K/Akt/mTOR signaling pathway activation was significantly suppressed in the doxazosin-treated group. The expression of HIF-1α and VEGF was also notably reduced by systemic doxazosin treatment.
Doxazosin exerts antiangiogenic actions in an experimental mouse model of CNV and may be a potential adjunctive therapy for neovascular age-related macular degeneration in humans.</description><identifier>ISSN: 1080-7683</identifier><identifier>EISSN: 1557-7732</identifier><identifier>DOI: 10.1089/jop.2016.0153</identifier><identifier>PMID: 27992238</identifier><language>eng</language><publisher>United States</publisher><subject>Angiogenesis Inhibitors - administration & dosage ; Angiogenesis Inhibitors - pharmacology ; Animals ; Choroidal Neovascularization - drug therapy ; Choroidal Neovascularization - pathology ; Disease Models, Animal ; Doxazosin - administration & dosage ; Doxazosin - pharmacology ; Lasers ; Male ; Mice ; Mice, Inbred C57BL</subject><ispartof>Journal of ocular pharmacology and therapeutics, 2017-01, Vol.33 (1), p.50-56</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c293t-59d546a07e52b9200d3d4dd913b51033a53deb0cdbd486a4a0ef441700d44bc3</citedby><cites>FETCH-LOGICAL-c293t-59d546a07e52b9200d3d4dd913b51033a53deb0cdbd486a4a0ef441700d44bc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27992238$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Guo, Jiaxian</creatorcontrib><creatorcontrib>Luo, Xueting</creatorcontrib><creatorcontrib>Liang, Jian</creatorcontrib><creatorcontrib>Xiao, Meichun</creatorcontrib><creatorcontrib>Sun, Xiaodong</creatorcontrib><title>Antiangiogenic Effects of Doxazosin on Experimental Choroidal Neovascularization in Mice</title><title>Journal of ocular pharmacology and therapeutics</title><addtitle>J Ocul Pharmacol Ther</addtitle><description>The present study was designed to evaluate the effects of doxazosin on experimental choroidal neovascularization (CNV) in mice.
Six- to 8-week-old male C57BL/6 mice were divided into a control group and a doxazosin-treated group (5 mg/kg, i.p., daily). Experimental CNV was induced by laser photocoagulation. Seven and 14 days after laser induction, fluorescein angiography, choroidal flat mounts, and histological studies were performed to evaluate the fluorescence leakage, area, and thickness of CNV lesions, respectively. In addition, western blot analysis was carried out to assess the inhibitory effects of doxazosin on the PI3K/Akt/mTOR signaling pathway and the expression levels of hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF), which are involved in CNV model.
Compared with the control group, the doxazosin-treated group demonstrated significantly less fluorescence leakage on day 7 and 14 after laser induction. Both the area and the thickness of CNV lesions in the doxazosin-treated group were significantly decreased. Mechanistically, PI3K/Akt/mTOR signaling pathway activation was significantly suppressed in the doxazosin-treated group. The expression of HIF-1α and VEGF was also notably reduced by systemic doxazosin treatment.
Doxazosin exerts antiangiogenic actions in an experimental mouse model of CNV and may be a potential adjunctive therapy for neovascular age-related macular degeneration in humans.</description><subject>Angiogenesis Inhibitors - administration & dosage</subject><subject>Angiogenesis Inhibitors - pharmacology</subject><subject>Animals</subject><subject>Choroidal Neovascularization - drug therapy</subject><subject>Choroidal Neovascularization - pathology</subject><subject>Disease Models, Animal</subject><subject>Doxazosin - administration & dosage</subject><subject>Doxazosin - pharmacology</subject><subject>Lasers</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><issn>1080-7683</issn><issn>1557-7732</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo90D1PwzAQgGELgSgURlaUkSXl_JXEY1XKh1Rg6cBmObZTXKVxiBNU-utx1cJ0Nzw66V6EbjBMMBTifu3bCQGcTQBzeoIuMOd5mueUnMYdCkjzrKAjdBnCGgBTyPA5GpFcCEJocYE-pk3vVLNyfmUbp5N5VVndh8RXyYPfqp0Prkl8k8y3re3cxja9qpPZp--8M3F7s_5bBT3UqnM71bsoo3912l6hs0rVwV4f5xgtH-fL2XO6eH96mU0XqSaC9ikXhrNMQW45KQUBMNQwYwSmJcdAqeLU2BK0KQ0rMsUU2IoxnEfIWKnpGN0dzrad_xps6OXGBW3rWjXWD0HigmMiABMaaXqguvMhdLaSbfxIdT8Sg9y3lLGl3LeU-5bR3x5PD-XGmn_9F4_-Av_mcE4</recordid><startdate>201701</startdate><enddate>201701</enddate><creator>Guo, Jiaxian</creator><creator>Luo, Xueting</creator><creator>Liang, Jian</creator><creator>Xiao, Meichun</creator><creator>Sun, Xiaodong</creator><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>201701</creationdate><title>Antiangiogenic Effects of Doxazosin on Experimental Choroidal Neovascularization in Mice</title><author>Guo, Jiaxian ; Luo, Xueting ; Liang, Jian ; Xiao, Meichun ; Sun, Xiaodong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c293t-59d546a07e52b9200d3d4dd913b51033a53deb0cdbd486a4a0ef441700d44bc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Angiogenesis Inhibitors - administration & dosage</topic><topic>Angiogenesis Inhibitors - pharmacology</topic><topic>Animals</topic><topic>Choroidal Neovascularization - drug therapy</topic><topic>Choroidal Neovascularization - pathology</topic><topic>Disease Models, Animal</topic><topic>Doxazosin - administration & dosage</topic><topic>Doxazosin - pharmacology</topic><topic>Lasers</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Guo, Jiaxian</creatorcontrib><creatorcontrib>Luo, Xueting</creatorcontrib><creatorcontrib>Liang, Jian</creatorcontrib><creatorcontrib>Xiao, Meichun</creatorcontrib><creatorcontrib>Sun, Xiaodong</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>Journal of ocular pharmacology and therapeutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Guo, Jiaxian</au><au>Luo, Xueting</au><au>Liang, Jian</au><au>Xiao, Meichun</au><au>Sun, Xiaodong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Antiangiogenic Effects of Doxazosin on Experimental Choroidal Neovascularization in Mice</atitle><jtitle>Journal of ocular pharmacology and therapeutics</jtitle><addtitle>J Ocul Pharmacol Ther</addtitle><date>2017-01</date><risdate>2017</risdate><volume>33</volume><issue>1</issue><spage>50</spage><epage>56</epage><pages>50-56</pages><issn>1080-7683</issn><eissn>1557-7732</eissn><abstract>The present study was designed to evaluate the effects of doxazosin on experimental choroidal neovascularization (CNV) in mice.
Six- to 8-week-old male C57BL/6 mice were divided into a control group and a doxazosin-treated group (5 mg/kg, i.p., daily). Experimental CNV was induced by laser photocoagulation. Seven and 14 days after laser induction, fluorescein angiography, choroidal flat mounts, and histological studies were performed to evaluate the fluorescence leakage, area, and thickness of CNV lesions, respectively. In addition, western blot analysis was carried out to assess the inhibitory effects of doxazosin on the PI3K/Akt/mTOR signaling pathway and the expression levels of hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF), which are involved in CNV model.
Compared with the control group, the doxazosin-treated group demonstrated significantly less fluorescence leakage on day 7 and 14 after laser induction. Both the area and the thickness of CNV lesions in the doxazosin-treated group were significantly decreased. Mechanistically, PI3K/Akt/mTOR signaling pathway activation was significantly suppressed in the doxazosin-treated group. The expression of HIF-1α and VEGF was also notably reduced by systemic doxazosin treatment.
Doxazosin exerts antiangiogenic actions in an experimental mouse model of CNV and may be a potential adjunctive therapy for neovascular age-related macular degeneration in humans.</abstract><cop>United States</cop><pmid>27992238</pmid><doi>10.1089/jop.2016.0153</doi><tpages>7</tpages></addata></record> |
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| subjects | Angiogenesis Inhibitors - administration & dosage Angiogenesis Inhibitors - pharmacology Animals Choroidal Neovascularization - drug therapy Choroidal Neovascularization - pathology Disease Models, Animal Doxazosin - administration & dosage Doxazosin - pharmacology Lasers Male Mice Mice, Inbred C57BL |
| title | Antiangiogenic Effects of Doxazosin on Experimental Choroidal Neovascularization in Mice |
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