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Lu Chen, MD, PhD; Syed Huq, MD; Humphrey Gardner, MD; Antonin R. de Fougerolles, PhD; Stefano Barabino, MD; M. Reza Dana, MD, MSc, MPH

Arch Ophthalmol. 2007;125(6):783-788.

Objective  To investigate the role of very late antigen 1 (VLA-1) (also known as integrin receptor ₁β₁) 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.

Author Affiliations: Laboratory of Immunology, Schepens Eye Research Institute and Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Mass (Drs Chen, Huq, Barabino, and Dana); Research Pathology, Biogen Idec (Drs Gardner and de Fougerolles), Cambridge, Mass.

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