title: Vascular Endothelial Growth Factor Receptor 1 morpholino increases graft survival in a murine penetrating keratoplasty model.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Ophthalmology, University of Utah School of Medicine, Salt Lake City, Utah, USA.
authors.forename: Yang Kyung
authors.initials: YK
authors.lastname: Cho
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Zhang
authors.forename: Hironori
authors.initials: H
authors.lastname: Uehara
authors.forename: Jason R
authors.initials: JR
authors.lastname: Young
authors.forename: Bonnie
authors.initials: B
authors.lastname: Archer
authors.forename: Balamurali
authors.initials: B
authors.lastname: Ambati
mesh_terms: D000818:Animals; D003315:Cornea / Q000502:physiology; D016510:Corneal Neovascularization / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004357:Drug Synergism; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006085:Graft Survival / Q000187:drug effects*; D015948:Keratoplasty, Penetrating; D042583:Lymphangiogenesis / Q000187:drug effects; D042601:Lymphatic Vessels / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D060172:Morpholinos / Q000627:therapeutic use*; D014222:Triamcinolone Acetonide / Q000627:therapeutic use; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D005938:Glucocorticoids; D060172:Morpholinos; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; C501163:Flt1 protein, mouse; D040281:Vascular Endothelial Growth Factor Receptor-1; D014222:Triamcinolone Acetonide