Inhibition of Corneal Neovascularization by Hydrazinocurcumin

Purpose: To investigate the effect of hydrazinocurcumin on a human vascular endothelial growth factor (VEGF)-induced corneal neovascularization in rabbit model.Methods: Murine corneal neovascularization (CorNV) was induced via two intrastromal implantations of VEGF polymer 2 mm from the limbus. Hydrazinocurcumin was administered topically on the cornea 4 times daily for 7 days. The therapeutic effects of hydrazinocurcumin were evaluated daily using slitlamp. At the end of the treatment, the corneas were harvested for H&E staining, masson trichrome staining, immuno-histochemical study, and semi quantification reverse transcription polymerase chain reaction (RT-PCR) was utilized for measurement of inflammation-related molecules.Results: Topical application of hydrazinocurcumin had significant therapeutic effects on CorNV Hydrazinocurcumin extract treatment was more effective in suppressing CorNV in terms of vessel length and levels of cluster of differentiation 31 (CD31) proteins or angiogenesis-related genes such as VEGF, matrix metalloproteinase-2 (MMP2) and matrix metalloproteinase-9 (MMP9). The average length of vessels in hydrazinocurcumin-treated group was only 17 % of that in the control group. Hydrazinocurcumin also inhibited inflammation more markedly by more effectively inhibiting mononuclear and polymorphonuclear cell infiltration into the corneal stroma and reducing levels of stromal cell-derived factor-1 (SDF1), tumor necrosis factor-alpha (TNFα) and macrophage inflammatory protein-3 (MIP3a). In addition, the corneas of hydrazinocurcumin group had a more regular and compact architecture of collagen with thinner corneal thickness than those of the untreated group.Conclusion: Hydrazinocurcumin inhibited human vascular endothelial growth factor (VEGF)-induced rabbit corneal neovascularization and thus can potentially be used for its treatment.Keywords: Hydrazinocurcumin, Corneal neovascularization, Inflammation, Vascular endothelial growth factor, Corneal thicknes