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Guangyu Li, Gyeong Jin Kang, Narae Lee, Anna email@example.com Gong, Yasuyuki Yokosaki, Lu Chen; Combined blockade of VEGFR-3 and integrin alpha9beta1 inhibits corneal lymphangiogenesis and valvulogenesis in vivo and promotes high-risk graft survival. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5733.
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Corneal transplantation is the last hope for vision restoration for patients who are blind from corneal diseases. The rejection rate of high-risk grafts can be 50-90%, irrespective of current treatment modalities. VEGFR-3 (vascular endothelial growth factor receptor-3) is known for its critical role in lymphangiogenesis (LG), and we recently reported that integrin alpha9beta1 mediates luminal valve formation (valvulogenesis, VG) inside the lymphatic vessels during corneal LG. In this study, the effects of combined blockade of VEGFR-3 and integrin alpha9beta1 were evaluated after high-risk corneal transplantation.
High-risk corneal transplantation was performed between fully mismatched BALB/c (donor) and Prox-1-GFP (green fluorescent protein) mice in C57BL/6 background (recipient). The recipient mice were randomized to receive neutralizing antibodies of VEGFR-3 (kindly provided by Eli Lilly and Company) and integrin alpha9beta1. Processes of corneal LG and VG were assessed in vivo by our live imaging system, and corneal grafts were evaluated by ophthalmic slit-lamp microscopy as well.
Combined blockade of VEGFR-3 and integrin alpha9beta1 significantly suppressed both LG and VG after corneal transplantation, and this treatment led to a markedly promoted survival rate in the high-risk setting.
This study offers new insights into high-risk transplant rejection. It may also provide a novel pharmaceutical therapy to treat other lymphatic- and immune-related diseases in the body.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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