title: Flt23k nanoparticles offer additive benefit in graft survival and anti-angiogenic effects when combined with triamcinolone.
abstract: OBJECTIVE
  To determine if nanoparticles delivering plasmids expressing Flt23k (an anti-VEGF intraceptor) can enhance murine cornea transplant survival and whether their effect is synergistic with steroid therapy.
  
  
  METHODS
  Biodegradable PLGA Flt23k loaded or blank nanoparticles were prepared using the emulsion solvent evaporation
  
  
  METHODS
  Graft survival, corneal neovascularization, and corneal lymphangiogenesis were compared among the Flt23k nanoparticles, blank nanoparticles, triamcinolone acetonide, and PBS groups following subconjunctival injection in mice that underwent penetrating keratoplasty. Graft survival, corneal neovascularization, and corneal lymphangiogenesis in a group treated with both nanoparticles and steroid therapy were also analyzed.
  
  
  RESULTS
  The Flt23k nanoparticle group showed less neovascularization, lymphangiogenesis, and graft failure compared with the PBS control group (P < 0.01). The 2-month graft survival rate was 20% in the Flt23k nanoparticle group with no grafts surviving in the PBS group. When the Flt23k nanoparticle was combined with steroid therapy, a significant increase in graft survival was seen compared with both steroid treatment alone (P < 0.05) and steroid combined with blank nanoparticle treatment (P < 0.05). The 2-month graft survival rate was 91.6% in the combination group compared with 47.6% in the triamcinolone-only group and 42.4% in the triamcinolone plus blank nanoparticle group.
  
  
  CONCLUSIONS
  Anti-VEGF nanoparticles (Flt23k) have a significant effect on decreasing neovascularization and lymphangiogenesis, resulting in increased graft survival in penetrating keratoplasty. This beneficial effect is synergistically enhanced with steroid treatment.
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Utah, Salt Lake City, Utah 84132, USA.
authors.forename: Yang Kyung
authors.initials: YK
authors.lastname: Cho
authors.forename: Hironori
authors.initials: H
authors.lastname: Uehara
authors.forename: Jason R
authors.initials: JR
authors.lastname: Young
authors.forename: Puneet
authors.initials: P
authors.lastname: Tyagi
authors.forename: Uday B
authors.initials: UB
authors.lastname: Kompella
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Zhang
authors.forename: Ling
authors.initials: L
authors.lastname: Luo
authors.forename: Nirbhai
authors.initials: N
authors.lastname: Singh
authors.forename: Bonnie
authors.initials: B
authors.lastname: Archer
authors.forename: Balamurali K
authors.initials: BK
authors.lastname: Ambati
mesh_terms: D020533:Angiogenesis Inhibitors / Q000235:genetics / Q000494:pharmacology*; D000818:Animals; D016510:Corneal Neovascularization / Q000188:drug therapy*; D005938:Glucocorticoids / Q000494:pharmacology*; D006085:Graft Survival / Q000187:drug effects*; D042583:Lymphangiogenesis / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D053758:Nanoparticles; D014222:Triamcinolone Acetonide / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
chemical_list: D020533:Angiogenesis Inhibitors; D005938:Glucocorticoids; D042461:Vascular Endothelial Growth Factor A; D014222:Triamcinolone Acetonide