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L. Chen, H. Gardner, A.R. de Fougerolles, S. Barabino, R. Dana; Very Late Antigen (VLA)–1 Blockade Leads to Markedly Enhanced Survival of Corneal Allografts . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5867.
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Very late antigen–1 (VLA–1), also known as integrin receptor alpha1 beta1, is a collagen binding integrin that mediates T cell proliferation and cytokine secretion. Blockade of this receptor’s function has been shown to ameliorate inflammation in certain immuno–inflammatory disease states, such as rheumatoid arthritis. However, there have been no studies to date on the role of VLA–1 on transplant survival. The purpose of this study was to investigate the role of VLA–1 in the inflammation associated with corneal transplantation, and assess corneal graft survival in VLA–1 deficiency.
To assess immune cell infiltration post transplantation, allodisparate corneal transplantation was performed between normal C57BL/6 and BALB/c mice. Graft recipients (BALB/c mice) were treated with either anti–VLA–1 or isotype control antibodies and the grafted eyes were harvested at various time points for immunofluorescent microscopic studies. To investigate the effect of VLA–1 deficiency on transplantation–associated vasculogenesis, corneal buttons from normal C57BL/6 mice were transplanted into VLA–1 knockout BALB/c mice, and the grafted eyes were harvested at 7 days post transplantation and stained for blood and lymphatic vessels. Furthermore, corneal graft survival was assessed in VLA–1 knockout mice.
Anti–VLA–1 antibody treatment leads to a profound reduction in the cellular (granulocytic and monocytic) infiltrate post– transplantation. In addition, VLA–1 knockouts demonstrated greatly suppressed corneal angiogenesis and lymphangiogenesis,as well as significant improvement in graft survival.
VLA–1 blackade markedly reduces inflammation, and inflammation–induced tissue responses including vasculogenesis, associated with corneal transplantation, and promotes allograft survival.
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