Purpose
Corneal neovascularization (NV) contributes significantly to ocular disease and vision loss. Pathological ingrowth of blood vessels from the limbal vascular plexus into the cornea, results from infection, extended use of contact lens, direct or chemical trauma, or immunologic disease. Epithelial membrane protein 2 (EMP2), a member of GAS3/PMP22 tetraspan protein family, is expressed in the corneal epithelium, and controls VEGF expression in ocular epithelial cell lines. The goal of this study is to examine the relationship between EMP2 and neovascularization of the cornea in a burn model.
Methods
Corneal NV was induced in 6-8 week old female Balb/c mice using a NaOH burn method. Mice were treated with a recombinant anti-EMP2 or control antibody via subconjunctival injection immediately after the corneal burn. Animals were photographically imaged and clinically evaluated to determine the extent of NV. Seven days post treatment, the eyes were enucleated and immunohistochemical studies were performed to identify the vasculature using antibodies against CD34.
Results
Subconjunctival injections of anti-EMP2 antibody, but not control antibody, significantly decreased EMP2 expression in the cornea epithelium at day 7. Clinically, less corneal NV was observed in the eyes that received the subconjunctival injection of anti-EMP2 antibody than controls without antibody or with a control antibody (p< 0.03). In the anti- EMP2 treated corneas, as compared to the controls, less vasculature was identified using histologic analysis and fewer vessels were identified using anti-CD34 immunohistochemistry.
Conclusions
Subconjunctival injections of anti-EMP2 reduce the corneal epithelial expression of EMP2 for at least one week. Reduction of corneal NV following corneal burn is observed by blocking and reducing EMP2 surface expression on the ocular surface. Modulation of EMP2 expression may provide a new method of preventing corneal neovascularization following injury.
Keywords: 609 neovascularization •
480 cornea: basic science •
482 cornea: epithelium