Abstract
Purpose: :
Recently, use of topical bevacizumab (Avastin), a recombinant humanized monoclonal IgG1 antibody that inhibits human vascular endothelial growth factor (VEGF), has been considered for the treatment of corneal neovascularization. This study investigated whether bevacizumab, a full-length anti-VEGF antibody, would be able to penetrate the cornea after topical application.
Methods: :
Corneal penetration of bevacizumab was examined in a mouse model (BALB/c). Bevacizumab 1% (10mg/ml) was topically applied three times a day to the corneas of mice (N=30). Animals were divided in two groups: the first group with intact corneas and without any obvious pathology or vascularization; the second group with corneal neovascularization induced by micropellet containing 80 ng of basic fibroblast growth factor (bFGF). To evaluate corneal penetration in both groups, animals were euthanized at 12, 24 hours, and 3, 5, and 7 days after the initiation of topical treatment for immunohistochemical analyses. Donkey anti-human IgG labeled with Cy3 was used for bevacizumab immunoreactivity detection.
Results: :
Bevacizumab immunoreactivity was barely found in the corneal stroma in mice with intact corneas even after 7 days of topical administration. Application of bevacizumab in mice with corneal neovascularization, however, showed high immunoreactivity in the all layers of the cornea.
Conclusions: :
The results clearly demonstrate that bevacizumab can penetrate the neovascularized cornea after topical application.
Keywords: neovascularization • cornea: basic science • vascular endothelial growth factor