| Vascular Endothelial Growth Factor Receptor 1 morpholino increases graft survival in a murine penetrating keratoplasty model. | |
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MedLine Citation:
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PMID: 23150613 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE: This study sought to determine whether a Vascular Endothelial Growth Factor Receptor 1 (VEGFR1)-specific morpholino (MO) could decrease neovascularization, thereby enhancing murine cornea transplant survival, and if this effect is synergistic with steroid therapy. METHODS: Graft survival, corneal neovascularization, and corneal lymphangiogenesis were compared among the VEGFR1_MO, STD MO and PBS groups following subconjunctival injection in mice that underwent normal risk penetrating keratoplasty (NR PK) and high-risk penetrating keratoplasty (HR PK). Graft survival, corneal neovascularization, and corneal lymphangiogenesis in groups treated with both VEGFR1_MO and steroid therapy were also analyzed in HR PK. RESULTS: In NR PK, the VEGFR1_MO decreased angiogenesis, lymphangiogenesis, and increased graft survival compared with the PBS group (P = 0.055, P = 0.003, P = 0.043, respectively). In HR PK, VEGFR1_MO decreased angiogenesis, lymphangiogenesis, and increased graft survival compared with the STD MO (P = 0.000, P = 0.000, P = 0.029, respectively) and PBS groups (P = 0.004, P = 0.002, P = 0.024). In HR PK, when the VEGFR1_MO was combined with steroid therapy, a significant increase in graft survival was seen compared with steroid treatment alone (P = 0.045). The 2-month graft survival rate for HR PK was 27% in the combination group compared with 0% in the triamcinolone only group. CONCLUSIONS: VEGFR1_MO decreased angiogenesis and lymphangiogenesis, resulting in increased graft survival in both NR PK and HR PK. This beneficial effect is synergistically enhanced with steroid treatment in HR PK. |
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Authors:
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Yang Kyung Cho; Xiaohui Zhang; Hironori Uehara; Jason R Young; Bonnie Archer; Balamurali Ambati |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2012-12-19 |
Journal Detail:
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Title: Investigative ophthalmology & visual science Volume: 53 ISSN: 1552-5783 ISO Abbreviation: Invest. Ophthalmol. Vis. Sci. Publication Date: 2012 Dec |
Date Detail:
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Created Date: 2012-12-20 Completed Date: 2013-02-14 Revised Date: 2013-05-15 |
Medline Journal Info:
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Nlm Unique ID: 7703701 Medline TA: Invest Ophthalmol Vis Sci Country: United States |
Other Details:
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Languages: eng Pagination: 8458-71 Citation Subset: IM |
Affiliation:
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Department of Ophthalmology, University of Utah School of Medicine, Salt Lake City, Utah, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cornea / physiology Corneal Neovascularization / metabolism, pathology, prevention & control* Disease Models, Animal* Drug Synergism Female Glucocorticoids / therapeutic use Graft Survival / drug effects* Keratoplasty, Penetrating* Lymphangiogenesis / drug effects Lymphatic Vessels / drug effects, physiology Male Mice Mice, Inbred BALB C Mice, Inbred C57BL Morpholinos / therapeutic use* Triamcinolone Acetonide / therapeutic use Vascular Endothelial Growth Factor A / metabolism Vascular Endothelial Growth Factor Receptor-1 / genetics*, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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NIHEY017950//PHS HHS; P30 EY014800/EY/NEI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Glucocorticoids; 0/Morpholinos; 0/Vascular Endothelial Growth Factor A; 0/vascular endothelial growth factor A, mouse; 76-25-5/Triamcinolone Acetonide; EC 2.7.10.1/Flt1 protein, mouse; EC 2.7.10.1/Vascular Endothelial Growth Factor Receptor-1 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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