Very Late Antigen-1 Mediates Corneal Lymphangiogenesis

PURPOSE. To investigate the specific role of very late antigen-1 (VLA-1; also known as integrin alpha 1 beta 1) in corneal inflammatory lymphangiogenesis in vivo and lymphatic endothelial cell functions in vitro. METHODS. A standard suture-induced corneal inflammatory lymphangiogenesis model was used in normal adult BALB/c mice to test the effect of systemic administration of VLA-1-neutralizing antibody on lymphatic formation and macrophage infiltration in vivo. Additionally, a human lymphatic endothelial cell culture system was used to examine the effect of VLA-1 gene depletion on lymphatic endothelial cell functions in vitro using small interfering RNAs. RESULTS. These data demonstrated, for the first time, that VLA-1 blockade significantly suppressed corneal lymphangiogenesis and macrophage infiltration during inflammation. Moreover, VLA-1 gene depletion led to a marked inhibition of lymphatic endothelial cell processes of adhesion, proliferation, and capillary tube formation. CONCLUSIONS. These novel findings together indicate that VLA-1 is critically involved in the processes of lymphangiogenesis. Further investigation on this factor may provide novel therapies for corneal inflammation, transplant rejection, and other lymphatic-related disorders in the body. (Invest Ophthalmol Vis Sci. 2011;52:4808-4812) DOI:10.1167/iovs.10-6580