Document Detail

Vascular Endothelial Growth Factor Receptor 1 morpholino increases graft survival in a murine penetrating keratoplasty model.
MedLine Citation:
PMID:  23150613     Owner:  NLM     Status:  MEDLINE    
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.
Yang Kyung Cho; Xiaohui Zhang; Hironori Uehara; Jason R Young; Bonnie Archer; Balamurali Ambati
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-12-19
Journal Detail:
Title:  Investigative ophthalmology & visual science     Volume:  53     ISSN:  1552-5783     ISO Abbreviation:  Invest. Ophthalmol. Vis. Sci.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-20     Completed Date:  2013-02-14     Revised Date:  2014-08-14    
Medline Journal Info:
Nlm Unique ID:  7703701     Medline TA:  Invest Ophthalmol Vis Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  8458-71     Citation Subset:  IM    
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MeSH Terms
Cornea / physiology
Corneal Neovascularization / metabolism,  pathology,  prevention & control*
Disease Models, Animal*
Drug Synergism
Glucocorticoids / therapeutic use
Graft Survival / drug effects*
Keratoplasty, Penetrating*
Lymphangiogenesis / drug effects
Lymphatic Vessels / drug effects,  physiology
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
Reg. No./Substance:
0/Glucocorticoids; 0/Morpholinos; 0/Vascular Endothelial Growth Factor A; 0/vascular endothelial growth factor A, mouse; EC protein, mouse; EC Endothelial Growth Factor Receptor-1; F446C597KA/Triamcinolone Acetonide

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