June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Combined blockade of VEGFR-3 and integrin alpha9beta1 inhibits corneal lymphangiogenesis and valvulogenesis in vivo and promotes high-risk graft survival
Guangyu Li; Gyeong Jin Kang; Narae Lee; Anna annagong@berkeley.edu Gong; Yasuyuki Yokosaki; Lu Chen
Author Affiliations & Notes
  • Guangyu Li
    Graduate Group in Vision Science, University of California at Berkeley, Berkeley, California, United States
    Center for Eye Disease and Development, Program in Vision Science, and School of Optometry, , University of California at Berkeley, Berkeley, California, United States
  • Gyeong Jin Kang
    Graduate Group in Vision Science, University of California at Berkeley, Berkeley, California, United States
    Center for Eye Disease and Development, Program in Vision Science, and School of Optometry, , University of California at Berkeley, Berkeley, California, United States
  • Narae Lee
    Graduate Group in Vision Science, University of California at Berkeley, Berkeley, California, United States
    Center for Eye Disease and Development, Program in Vision Science, and School of Optometry, , University of California at Berkeley, Berkeley, California, United States
  • Anna annagong@berkeley.edu Gong
    Graduate Group in Vision Science, University of California at Berkeley, Berkeley, California, United States
    Center for Eye Disease and Development, Program in Vision Science, and School of Optometry, , University of California at Berkeley, Berkeley, California, United States
  • Yasuyuki Yokosaki
    Cell-Matrix Frontier Laboratory, Biomedical Research Unit, Hiroshima University, Hiroshima, Japan
  • Lu Chen
    Graduate Group in Vision Science, University of California at Berkeley, Berkeley, California, United States
    Center for Eye Disease and Development, Program in Vision Science, and School of Optometry, , University of California at Berkeley, Berkeley, California, United States
  • Footnotes
    Commercial Relationships   Guangyu Li, None; Gyeong Jin Kang, None; Narae Lee, None; Anna Gong, None; Yasuyuki Yokosaki, None; Lu Chen, None
  • Footnotes
    Support  This work is supported in part by research grants from NIH, DoD and University of California at Berkeley (LC).
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 5733. doi:
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      Guangyu Li, Gyeong Jin Kang, Narae Lee, Anna annagong@berkeley.edu 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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Abstract

Purpose : 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.

Methods : 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.

Results : 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.

Conclusions : 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.

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
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Copyright © 2024 Association for Research in Vision and Ophthalmology.
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