KH906, a recombinant human VEGF receptor fusion protein, is a new effective topical treatment for corneal neovascularization
نویسندگان
چکیده
PURPOSE The purpose of the current study was to investigate the effect of topical administration of KH906 on corneal neovascularization (NV). METHODS To induce corneal neovascularization, chemical cauterization of the corneas of the right eyes of forty-eight New Zealand white rabbits was performed by touching the central cornea with an 8-mm-diameter NaOH-soaked Whatman filter paper for 60 s. On the next day after modeling, the rabbits were randomly and equally divided into six groups: PBS control group, 0.1% dexamethasone group, 10 mg/ml Avastin group, 5 mg/ml KH906 group, 10 mg/ml KH906 group, and 20 mg/ml KH906 group. The rabbits in the six groups received topical administration of 50 μl of the different solutions on the cornea four times per day for 14 days. Corneal neovascularization was analyzed by slit-lamp biomicroscopy 10 and 14 days after chemical cauterization. Corneal fluorescein staining was performed to evaluate the extent of corneal epithelial defect on the 7th, 10th, and 14th days. The VEGF level of the cornea was evaluated by ELISA assay. RESULTS On the 10th and 14th days after chemical cauterization, the length of the longest new vessel and the areas of corneal neovascularization in all KH906-treated groups were significantly reduced compared to those of the PBS-treated group (p<0.05). The VEGF level of the cornea in all KH906-treated groups was significantly decreased compared to that of the PBS-treated group (p<0.05). Corneal fluorescein staining showed that KH906 had no effect on corneal epithelial healing. CONCLUSIONS Topical administration of KH906 significantly inhibited alkali burn-induced corneal neovascularization in rabbits. The new eye drops of KH906 may have a broad application for human corneal neovascularization in the near future.
منابع مشابه
Thrombospondin 1 inhibits inflammatory lymphangiogenesis by CD36 ligation on monocytes
Lymphangiogenesis plays an important role in tumor metastasis and transplant outcome. Here, we show that thrombospondin-1 (TSP-1), a multifunctional extracellular matrix protein and naturally occurring inhibitor of angiogenesis inhibits lymphangiogenesis in mice. Compared with wild-type mice, 6-mo-old TSP-1-deficient mice develop increased spontaneous corneal lymphangiogenesis. Similarly, in a ...
متن کاملFlt-1 intraceptors inhibit hypoxia-induced VEGF expression in vitro and corneal neovascularization in vivo.
PURPOSE To determine whether subunits of VEGF receptor-1 coupled with an endoplasmic reticulum retention signal can block hypoxia-induced upregulation of VEGF secretion in corneal epithelial cells and block murine corneal angiogenesis induced by corneal injury. METHODS Human corneal epithelial cells, transfected with plasmids encoding Flt23K or Flt24K (the VEGF-binding domains of the Flt-1 re...
متن کاملInhibition of inflammatory corneal angiogenesis by TNP-470.
PURPOSE To determine the efficacy of the angiogenic inhibitor TNP-470 on inflammatory corneal neovascularization. Topical and systemic delivery of the drug were investigated in a murine model as well as inhibition of endothelial cell proliferation in vitro and in vivo. METHODS The effect of TNP-470 on VEGF- and bFGF-stimulated bovine capillary endothelial (BCE) cell proliferation was evaluate...
متن کاملTopical bevacizumab therapy for corneal neovascularization.
Angiogenesis has been defined as the formation of new blood vessels from preexisting vascular structures. Corneal neovascularization (NV) occurs when the balance between angiogenic and antiangiogenic factors shifts toward angiogenic factors. Vascular endothelial growth factor (VEGF) has been found to be a significant angiogenic factor in corneal NV in human and animal models. Therapy specifical...
متن کاملCloning, Expression and Characterization of Recombinant Exotoxin A-Flagellin Fusion Protein as a New Vaccine Candidate against Pseudomonas aeruginosa Infections
Background: Infections due to Pseudomonas aeruginosa are among the leading causes of morbidity and mortality in patients who suffer from impaired immune responses and chronic diseases such as cystic fibrosis. At present, aggressive antibiotic therapy is the only choice for management of P. aeruginosa infections, but emergence of highly resistant strains necessitated the development of novel alt...
متن کامل