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Meng Shi, Ziya Zhang, Guangyu Li, Yasuyuki Yokosaki, David G. Hwang, Lu Chen; Combined blockade of VEGFR-3 and Itga-9 promotes lamellar corneal transplant survival. Invest. Ophthalmol. Vis. Sci. 2018;59(9):508.
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© ARVO (1962-2015); The Authors (2016-present)
Lamellar corneal transplantation is an innovative surgical procedure that replaces partial thickness cornea and has evolved as a new trend to treat corneal stromal disorders. We have recently reported that this procedure induces lymphangiogenesis (LG) and valvulogenesis (VG), which are mediators of transplant rejection. In this study, we investigated the effects of a combined blockade of VEGFR-3 (vascular endothelial growth factor receptor-3) and Itga-9 (integrin alpha9beta1) on the processes of LG and VG and graft survival after lamellar transplantation.
Lamellar 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 Itga-9. Processes of corneal LG and VG were assessed in vivo by our advanced live imaging system, and lamellar grafts were evaluated by ophthalmic slit-lamp microscopy as well.
Combined blockade of VEGFR-3 and Itga-9 markedly inhibited both LG and VG after lamellar transplantation. This treatment also promoted graft survival.
This study not only offers new insights into lamellar transplant rejection but also provides a novel strategy to manage it and possibly other lymphatic- and immune-related diseases in the body.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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