Abstract
Abstract: :
Purpose: Very Late Antigen–1 (VLA–1), also known as integrin receptor a1b1 , 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 many immuno–inflammatory disease states, such as rheumatoid arthritis.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 post Anti–VLA–1 therapy. Methods: Donor corneal grafts harvested from C57BL/6 mice were transplanted into allodisparate BALB/c mice eyes. Graft recipients were treated with either Anti VLA–1 or isotype control antibodies. Grafted eyes were harvested at 1, 7, 14, and 28 days post transplantation, and immune cell infiltrate was assessed. Furthermore, corneal graft survival was assessed after 4 weeks of either Anti–VLA–1 or isoantibody therapy. Finally, survival of allografts was studied in VLA–1 knockout (KO) recipient mice. Results: Compared with Isoantibody treatment, Anti–VLA–1 Antibody therapy lead to a profound reduction in the cellular infiltrate and edema post transplantation. Further characterization of the immune cells revealed that Anti–VLA–1 treatment markedly reduced the infiltration of granulocytes as well as monocytes into the graft Furthermore, when compared with Isoantibody treatment, Anti–VLA–1 therapy significantly improves survival of corneal allografts (100% in Anti–VLA–1 treatment group vs. 50% survival Isoantibody group; P<0.01). Similarly, corneal graft survival in VLA–1 KO mice was significantly higher when compared with wildtype allograft recipients (95% vs 40%: P<0.01). Conclusions: Anti–VLA–1 therapy markedly reduces inflammation associated with corneal transplantation. Anti–VLA–1 therapy also greatly improves corneal allograft survival and may prove to be a novel molecular anti–rejection strategy.
Keywords: cornea: basic science • inflammation • transplantation