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Xiaohui Zhang, ; Targeted Flt23k Nanoparticles Increase Graft Survival in a Murine High-Risk Penetrating Keratoplasty Model. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1536.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose This study is to determine if targeted nanoparticles delivering plasmids expressing Flt23k (an anti-VEGF intraceptor) could decrease neovascularization, thereby enhancing murine high-risk penetrating keratoplasty (PKP) survival.
Methods RGD-functionalized Biodegradable PLGA Flt23k loaded (RGD.Flt23k.NP) or blank nanoparticles (RGD.Bk.NP) were prepared using the emulsion solvent evaporation method. Age and gender matched corneas were transplanted from male 6-8 weeks old C57BL/6 donors to BALB/c recipients with suture-induced vascularized high-risk corneal beds. The transparency of corneal graft was evaluated by slit lamp biomicroscopy. Corneal whole mounts were evaluated by EVOS® fluorescent microscopy. Graft survival, corneal neovascularization, and corneal lymphangiogenesis were compared among the high dose RGD.Flt23k.NP, low dose RGD.Flt23k.NP, RGD.Bk.NP, and PBS groups following subconjunctival injection in mice that underwent high-risk PKP. N=10 in each group. Statistical analysis was performed using ANOVA and unpaired two-tailed t-test.
Results The high dose RGD.Flt23k.NP group showed less neovascularization (p=0.000, p=0.003, p=0.003) and lymphangiogenesis (p=0.886, p=0.030, p=0.045) compared to the low dose RGD.Flt23k.NP, RGD.Bk.NP and PBS control groups, respectively. The low dose RGD.Flt23k.NP group showed less neovascularization but no statistical difference (p=0.126, p=0.110) and lymphangiogenesis (p=0.029, p=0.047), compared to the RGD.Bk.NP and PBS control group, respectively. The 2-month graft survival rate was 60%, 40%, 20%, and 10%, in the high dose RGD.Flt23k.NP, low dose RGD.Flt23k.NP, RGD.Bk.NP, and PBS groups, respectively. Compared with the two control groups, the low dose RGD.Flt23k.NP increases the survival rate, but only the high dose RGD.Flt23k.NP shows the significant difference (P < 0.05).
Conclusions Anti-VEGF nanoparticles (RGD.Flt23k.NP) have a significant effect on decreasing neovascularization and lymphangiogenesis, resulting in increased murine graft survival in high-risk PKP.
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