Inhibition of Pathologic Retinal Neovascularization by a Small Peptide Derived from Human Apolipoprotein(a)
To evaluate the effect of KV11, a novel 11-mer peptide from human apolipoprotein(a), against retinal neovascularization and to study its penetration and the possible toxicity to the retina. Wound-healing, a modified Boyden chamber, and MTS assays were used to evaluate the effect of KV11 on the migra...
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| Veröffentlicht in: | Investigative ophthalmology & visual science 2009-11, Vol.50 (11), p.5384-5395 |
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| container_title | Investigative ophthalmology & visual science |
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| creator | Zhao, Hui Jin, Huiyi Li, Qian Gu, Qing Zheng, Zhi Wu, Haixiang Ye, Siwei Sun, Xiaodong Xu, Xun Ho, Patrick C. P |
| description | To evaluate the effect of KV11, a novel 11-mer peptide from human apolipoprotein(a), against retinal neovascularization and to study its penetration and the possible toxicity to the retina.
Wound-healing, a modified Boyden chamber, and MTS assays were used to evaluate the effect of KV11 on the migration and proliferation of bovine retinal capillary endothelial cells (BRCECs) induced by vascular endothelial growth factor (VEGF) in vitro. The antiangiogenic effect of KV11 was also studied with a mouse model of oxygen-induced retinopathy. Then, FITC-labeled KV11 was injected into the vitreous of normal rabbits, the retinal penetration was determined by confocal laser-scanning microscope, and further confirmed by UPLC/MS analysis of KV11 in tissue extracts. Electrophysiological tests and histologic examinations were used to study the possible toxicity of KV11 against rabbit neuroretina after intravitreal administration.
KV11 inhibited VEGF-induced BRCEC migration but not proliferation and reduced the pathologic neovascularization in a mouse model, without affecting normal retinal vasculature. FITC-labeled KV11 appeared in the retina within 30 minutes after injection and diffused to all layers 3 hours later. The transfer of KV11 from the vitreous to the retina was confirmed by UPLC/MS data. Electrophysiologic tests and histologic examinations revealed no evident functional or morphologic abnormalities in rabbit neuroretina after KV11 injection.
It is concluded that the novel peptide KV11 is an effective inhibitor of retinal pathologic angiogenesis with a sufficient retinal penetration and a favorable safety profile and may provide a promising alternative for ocular antiangiogenic therapy. |
| doi_str_mv | 10.1167/iovs.08-3163 |
| format | Article |
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Wound-healing, a modified Boyden chamber, and MTS assays were used to evaluate the effect of KV11 on the migration and proliferation of bovine retinal capillary endothelial cells (BRCECs) induced by vascular endothelial growth factor (VEGF) in vitro. The antiangiogenic effect of KV11 was also studied with a mouse model of oxygen-induced retinopathy. Then, FITC-labeled KV11 was injected into the vitreous of normal rabbits, the retinal penetration was determined by confocal laser-scanning microscope, and further confirmed by UPLC/MS analysis of KV11 in tissue extracts. Electrophysiological tests and histologic examinations were used to study the possible toxicity of KV11 against rabbit neuroretina after intravitreal administration.
KV11 inhibited VEGF-induced BRCEC migration but not proliferation and reduced the pathologic neovascularization in a mouse model, without affecting normal retinal vasculature. FITC-labeled KV11 appeared in the retina within 30 minutes after injection and diffused to all layers 3 hours later. The transfer of KV11 from the vitreous to the retina was confirmed by UPLC/MS data. Electrophysiologic tests and histologic examinations revealed no evident functional or morphologic abnormalities in rabbit neuroretina after KV11 injection.
It is concluded that the novel peptide KV11 is an effective inhibitor of retinal pathologic angiogenesis with a sufficient retinal penetration and a favorable safety profile and may provide a promising alternative for ocular antiangiogenic therapy.</description><identifier>ISSN: 0146-0404</identifier><identifier>ISSN: 1552-5783</identifier><identifier>EISSN: 1552-5783</identifier><identifier>DOI: 10.1167/iovs.08-3163</identifier><identifier>PMID: 19515999</identifier><identifier>CODEN: IOVSDA</identifier><language>eng</language><publisher>Rockville, MD: ARVO</publisher><subject>Angiogenesis Inhibitors - chemical synthesis ; Angiogenesis Inhibitors - pharmacokinetics ; Angiogenesis Inhibitors - pharmacology ; Angiogenesis Inhibitors - toxicity ; Animals ; Apolipoproteins A - chemical synthesis ; Apolipoproteins A - pharmacokinetics ; Apolipoproteins A - pharmacology ; Apolipoproteins A - toxicity ; Biological and medical sciences ; Cattle ; Cell Movement - drug effects ; Cell Proliferation - drug effects ; Cells, Cultured ; Disease Models, Animal ; Endothelium, Vascular - cytology ; Eye and associated structures. Visual pathways and centers. Vision ; Female ; Fundamental and applied biological sciences. Psychology ; Injections ; Male ; Medical sciences ; Mice ; Mice, Inbred C57BL ; Microscopy, Confocal ; Ophthalmology ; Oxygen - toxicity ; Peptide Fragments - chemical synthesis ; Peptide Fragments - pharmacokinetics ; Peptide Fragments - pharmacology ; Peptide Fragments - toxicity ; Rabbits ; Retina - drug effects ; Retina - metabolism ; Retinal Neovascularization - chemically induced ; Retinal Neovascularization - metabolism ; Retinal Neovascularization - prevention & control ; Retinal Vessels - cytology ; Retinopathies ; Vertebrates: nervous system and sense organs ; Vitreous Body - metabolism ; Wound Healing - drug effects</subject><ispartof>Investigative ophthalmology & visual science, 2009-11, Vol.50 (11), p.5384-5395</ispartof><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c352t-125bee7fe3a13ae90ae8310341febe944f7e43b7b3b31ba4214582c11b8a4e173</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22063222$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19515999$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhao, Hui</creatorcontrib><creatorcontrib>Jin, Huiyi</creatorcontrib><creatorcontrib>Li, Qian</creatorcontrib><creatorcontrib>Gu, Qing</creatorcontrib><creatorcontrib>Zheng, Zhi</creatorcontrib><creatorcontrib>Wu, Haixiang</creatorcontrib><creatorcontrib>Ye, Siwei</creatorcontrib><creatorcontrib>Sun, Xiaodong</creatorcontrib><creatorcontrib>Xu, Xun</creatorcontrib><creatorcontrib>Ho, Patrick C. P</creatorcontrib><title>Inhibition of Pathologic Retinal Neovascularization by a Small Peptide Derived from Human Apolipoprotein(a)</title><title>Investigative ophthalmology & visual science</title><addtitle>Invest Ophthalmol Vis Sci</addtitle><description>To evaluate the effect of KV11, a novel 11-mer peptide from human apolipoprotein(a), against retinal neovascularization and to study its penetration and the possible toxicity to the retina.
Wound-healing, a modified Boyden chamber, and MTS assays were used to evaluate the effect of KV11 on the migration and proliferation of bovine retinal capillary endothelial cells (BRCECs) induced by vascular endothelial growth factor (VEGF) in vitro. The antiangiogenic effect of KV11 was also studied with a mouse model of oxygen-induced retinopathy. Then, FITC-labeled KV11 was injected into the vitreous of normal rabbits, the retinal penetration was determined by confocal laser-scanning microscope, and further confirmed by UPLC/MS analysis of KV11 in tissue extracts. Electrophysiological tests and histologic examinations were used to study the possible toxicity of KV11 against rabbit neuroretina after intravitreal administration.
KV11 inhibited VEGF-induced BRCEC migration but not proliferation and reduced the pathologic neovascularization in a mouse model, without affecting normal retinal vasculature. FITC-labeled KV11 appeared in the retina within 30 minutes after injection and diffused to all layers 3 hours later. The transfer of KV11 from the vitreous to the retina was confirmed by UPLC/MS data. Electrophysiologic tests and histologic examinations revealed no evident functional or morphologic abnormalities in rabbit neuroretina after KV11 injection.
It is concluded that the novel peptide KV11 is an effective inhibitor of retinal pathologic angiogenesis with a sufficient retinal penetration and a favorable safety profile and may provide a promising alternative for ocular antiangiogenic therapy.</description><subject>Angiogenesis Inhibitors - chemical synthesis</subject><subject>Angiogenesis Inhibitors - pharmacokinetics</subject><subject>Angiogenesis Inhibitors - pharmacology</subject><subject>Angiogenesis Inhibitors - toxicity</subject><subject>Animals</subject><subject>Apolipoproteins A - chemical synthesis</subject><subject>Apolipoproteins A - pharmacokinetics</subject><subject>Apolipoproteins A - pharmacology</subject><subject>Apolipoproteins A - toxicity</subject><subject>Biological and medical sciences</subject><subject>Cattle</subject><subject>Cell Movement - drug effects</subject><subject>Cell Proliferation - drug effects</subject><subject>Cells, Cultured</subject><subject>Disease Models, Animal</subject><subject>Endothelium, Vascular - cytology</subject><subject>Eye and associated structures. Visual pathways and centers. Vision</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Injections</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Microscopy, Confocal</subject><subject>Ophthalmology</subject><subject>Oxygen - toxicity</subject><subject>Peptide Fragments - chemical synthesis</subject><subject>Peptide Fragments - pharmacokinetics</subject><subject>Peptide Fragments - pharmacology</subject><subject>Peptide Fragments - toxicity</subject><subject>Rabbits</subject><subject>Retina - drug effects</subject><subject>Retina - metabolism</subject><subject>Retinal Neovascularization - chemically induced</subject><subject>Retinal Neovascularization - metabolism</subject><subject>Retinal Neovascularization - prevention & control</subject><subject>Retinal Vessels - cytology</subject><subject>Retinopathies</subject><subject>Vertebrates: nervous system and sense organs</subject><subject>Vitreous Body - metabolism</subject><subject>Wound Healing - drug effects</subject><issn>0146-0404</issn><issn>1552-5783</issn><issn>1552-5783</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpF0E1P3DAQh3ELUZUt7Y0z8gW1lQj1-GWTHBHlTUIUteVsjbMT1pDEkZ3dFf30TbqrcprLT_-RHsaOQJwBzPNvPqzTmSgyBXO1x2ZgjMxMXqh9NhOg55nQQh-wDyk9CyEBpHjPDqA0YMqynLGX227pnR986Hio-QMOy9CEJ1_xnzT4Dht-T2GNqVo1GP0f_AfdK0f-q8Wm4Q_UD35B_DtFv6YFr2No-c2qxY6f96HxfehjGMh3X_DrR_auxibRp909ZI9Xl78vbrK7H9e3F-d3WaWMHDKQxhHlNSkEhVQKpEKBUBpqclRqXeeklcudcgocagnaFLICcAVqglwdstPtbhVDSpFq20ffYny1IOzUzE7NrCjs1Gzkx1ver1xLize8izSCkx0YO2BTR-wqn_47KcVcSSlH93nrlv5pufGRbJoajbNgN5uNmZ5bowqt_gKp0oOv</recordid><startdate>20091101</startdate><enddate>20091101</enddate><creator>Zhao, Hui</creator><creator>Jin, Huiyi</creator><creator>Li, Qian</creator><creator>Gu, Qing</creator><creator>Zheng, Zhi</creator><creator>Wu, Haixiang</creator><creator>Ye, Siwei</creator><creator>Sun, Xiaodong</creator><creator>Xu, Xun</creator><creator>Ho, Patrick C. 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Visual pathways and centers. Vision</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Injections</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Microscopy, Confocal</topic><topic>Ophthalmology</topic><topic>Oxygen - toxicity</topic><topic>Peptide Fragments - chemical synthesis</topic><topic>Peptide Fragments - pharmacokinetics</topic><topic>Peptide Fragments - pharmacology</topic><topic>Peptide Fragments - toxicity</topic><topic>Rabbits</topic><topic>Retina - drug effects</topic><topic>Retina - metabolism</topic><topic>Retinal Neovascularization - chemically induced</topic><topic>Retinal Neovascularization - metabolism</topic><topic>Retinal Neovascularization - prevention & control</topic><topic>Retinal Vessels - cytology</topic><topic>Retinopathies</topic><topic>Vertebrates: nervous system and sense organs</topic><topic>Vitreous Body - metabolism</topic><topic>Wound Healing - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhao, Hui</creatorcontrib><creatorcontrib>Jin, Huiyi</creatorcontrib><creatorcontrib>Li, Qian</creatorcontrib><creatorcontrib>Gu, Qing</creatorcontrib><creatorcontrib>Zheng, Zhi</creatorcontrib><creatorcontrib>Wu, Haixiang</creatorcontrib><creatorcontrib>Ye, Siwei</creatorcontrib><creatorcontrib>Sun, Xiaodong</creatorcontrib><creatorcontrib>Xu, Xun</creatorcontrib><creatorcontrib>Ho, Patrick C. 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P</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibition of Pathologic Retinal Neovascularization by a Small Peptide Derived from Human Apolipoprotein(a)</atitle><jtitle>Investigative ophthalmology & visual science</jtitle><addtitle>Invest Ophthalmol Vis Sci</addtitle><date>2009-11-01</date><risdate>2009</risdate><volume>50</volume><issue>11</issue><spage>5384</spage><epage>5395</epage><pages>5384-5395</pages><issn>0146-0404</issn><issn>1552-5783</issn><eissn>1552-5783</eissn><coden>IOVSDA</coden><abstract>To evaluate the effect of KV11, a novel 11-mer peptide from human apolipoprotein(a), against retinal neovascularization and to study its penetration and the possible toxicity to the retina.
Wound-healing, a modified Boyden chamber, and MTS assays were used to evaluate the effect of KV11 on the migration and proliferation of bovine retinal capillary endothelial cells (BRCECs) induced by vascular endothelial growth factor (VEGF) in vitro. The antiangiogenic effect of KV11 was also studied with a mouse model of oxygen-induced retinopathy. Then, FITC-labeled KV11 was injected into the vitreous of normal rabbits, the retinal penetration was determined by confocal laser-scanning microscope, and further confirmed by UPLC/MS analysis of KV11 in tissue extracts. Electrophysiological tests and histologic examinations were used to study the possible toxicity of KV11 against rabbit neuroretina after intravitreal administration.
KV11 inhibited VEGF-induced BRCEC migration but not proliferation and reduced the pathologic neovascularization in a mouse model, without affecting normal retinal vasculature. FITC-labeled KV11 appeared in the retina within 30 minutes after injection and diffused to all layers 3 hours later. The transfer of KV11 from the vitreous to the retina was confirmed by UPLC/MS data. Electrophysiologic tests and histologic examinations revealed no evident functional or morphologic abnormalities in rabbit neuroretina after KV11 injection.
It is concluded that the novel peptide KV11 is an effective inhibitor of retinal pathologic angiogenesis with a sufficient retinal penetration and a favorable safety profile and may provide a promising alternative for ocular antiangiogenic therapy.</abstract><cop>Rockville, MD</cop><pub>ARVO</pub><pmid>19515999</pmid><doi>10.1167/iovs.08-3163</doi><tpages>12</tpages></addata></record> |
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| identifier | ISSN: 0146-0404 |
| ispartof | Investigative ophthalmology & visual science, 2009-11, Vol.50 (11), p.5384-5395 |
| issn | 0146-0404 1552-5783 1552-5783 |
| language | eng |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Angiogenesis Inhibitors - chemical synthesis Angiogenesis Inhibitors - pharmacokinetics Angiogenesis Inhibitors - pharmacology Angiogenesis Inhibitors - toxicity Animals Apolipoproteins A - chemical synthesis Apolipoproteins A - pharmacokinetics Apolipoproteins A - pharmacology Apolipoproteins A - toxicity Biological and medical sciences Cattle Cell Movement - drug effects Cell Proliferation - drug effects Cells, Cultured Disease Models, Animal Endothelium, Vascular - cytology Eye and associated structures. Visual pathways and centers. Vision Female Fundamental and applied biological sciences. Psychology Injections Male Medical sciences Mice Mice, Inbred C57BL Microscopy, Confocal Ophthalmology Oxygen - toxicity Peptide Fragments - chemical synthesis Peptide Fragments - pharmacokinetics Peptide Fragments - pharmacology Peptide Fragments - toxicity Rabbits Retina - drug effects Retina - metabolism Retinal Neovascularization - chemically induced Retinal Neovascularization - metabolism Retinal Neovascularization - prevention & control Retinal Vessels - cytology Retinopathies Vertebrates: nervous system and sense organs Vitreous Body - metabolism Wound Healing - drug effects |
| title | Inhibition of Pathologic Retinal Neovascularization by a Small Peptide Derived from Human Apolipoprotein(a) |
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