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H. Zhang, D. Yuen, L. Chen; Lymphatic Vessels Play a Major Role in High-Risk Corneal Transplant Rejection. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1558.
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Lymphatic research has progressed rapidly in recent years. In the immune reflex arc of the corneal transplantation immunity, the afferent pathway of lymphatics mediates the trafficking of antigen-presenting cells to draining lymph nodes, while the efferent pathway of blood vessels facilitates the infiltration of T cells to the grafts. To date, it still remains largely unknown which pathway plays a more significant role in mediating the rejection of high-risk transplants, which is the focus of this study.
High-risk corneal transplantation was performed between normal C57BL/6 (donor) and inflamed BALB/c (recipient) mice. The recipients were randomized to receive systemic injections of the VEGFR-3 (provided by ImClone Systems, New York) and VLA-1 neutralizing antibodies (provided by Covella Pharmaceuticals, Inc.) twice a week for up to 8 weeks after transplantation. Corneal blood vessels and graft opacity were evaluated by ophthalmic slit-lamp biomicroscopy. Additionally, whole-mount corneas were also sampled by the end of the study for immunofluorescent microscopic assays using the antibodies against CD31 (a panendothelial cell marker) and LYVE-1 (a lymphatic marker). The correlation between lymphatic or blood vessel distribution in the grafted corneas and the transplant outcomes (accepted or rejected) was analyzed.
Strong correlation was identified in the reduction of lymphatic vessel coverage and improvement of graft survival. In the accepted grafts of the treatment group, lymphatic vessels were almost abolished while blood vessels were only moderately suppressed.
Lymphatic vessels play a more significant role in mediating high-risk corneal transplant rejection. Therapeutic strategies targeting more specifically on the lymphatic pathway will provide an effective treatment for high-risk transplant rejection.
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