Very Late Antigen (VLA)-1 Blockade Markedly Promotes Survival of Corneal Allografts

Objective To investigate the role of very late antigen 1 (VLA-1) (also known as integrin receptor α 1 β 1 ) in corneal transplantation inflammation and allograft survival. Methods Cell infiltration and vasculogenesis (both angiogenesis and lymphangiogenesis) associated with allodisparate corneal transplantation were assessed in VLA-1–deficient conditions and controls by immunofluorescent microscopic studies. Corneal allograft survival was also assessed after anti–VLA-1 antibody treatment and in VLA-1 knockout recipient mice. Results Anti–VLA-1 antibody treatment leads to a profound reduction in the granulocytic, monocytic, and T-cell infiltration after corneal transplantation. In addition, corneal angiogenesis and lymphangiogenesis were both significantly suppressed in VLA-1 knockout mice. Remarkably, universal graft survival was observed in both anti–VLA-1 antibody treatment and knockout mice. Conclusions Very late antigen 1 blockade markedly reduces inflammation and inflammation-induced tissue responses, including vasculogenic responses, associated with corneal transplantation and promotes allograft survival. Clinical Relevance These studies offer insights into important integrin-mediated mechanisms of corneal transplant–related inflammation and provide possible new integrin-based immunotherapies for transplant rejection.