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Min S. Chang, Lung-Kun Yeh, Chia-Yang Liu, Ashwath Jayagopal; Enhancement of Corneal Healing by BVES Blocking Antibodies. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3567.
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BVES is a transmembrane protein that regulates tight junction (TJ) and adherens junction (AJ) formation. Furthermore, disruption of BVES level induces phenotypic changes in human corneal epithelial (HCE) cells that are associated with increased wound healing. These observations led us to postulate that antibodies blocking BVES will induce increased corneal healing.
Rabbit polyclonal antibodies (Y666) against BVES' extracellular region (aa 3-16) were generated. Cultured HCE cells and organ cultured mouse eyes were employed to determine the effects of these antibodies on cell adhesion (immunofluorescent staining), RhoA activation (Elisa assay), and mouse model corneal wound healing.
The immunofluorescent staining on confluent HCE cells for BVES with Y666 reveals a cell membrane pattern of distribution, similar to staining with intracellular domain BVES antibodies (846). Furthermore, Y666 is capable of binding to BVES in live HCE cells. Following antibody treatment of HCE cells, immuno-localization assays were performed to determine the subcellular distribution TJ and AJ proteins. TJ and AJ remained at the cell membrane following Y666 treatment even at regions of disrupted cell adhesion. The effects of Y666 antibodies on corneal wound healing were evaluated using a mouse model. Following injury, eyes cultured in the presence of Y666 exhibited faster healing (P <0.05) compared to untreated and 846 corneas. Disruption of BVES is associated with increased active RhoA increased cellular motility. However, Y666 did not alter RhoA activation.
These findings verify the extracellular domain of BVES as a therapeutic target to induce corneal wound healing.
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