title: Angiopoietin-2 Blockade Promotes Survival of Corneal Transplants.
abstract: Corneal transplantation remains the last hope for vision restoration, and lymphangiogenesis (LG) is a primary mediator of transplant rejection. This study was to investigate the specific role of angiopoietin-2 (Ang-2) in transplantation-associated LG and graft rejection.
  
  
  
  Orthotopic corneal transplantation was performed between fully mismatched C57BL/6 (donor) and BALB/c (recipient) mice to assess the effects of Ang-2 blockade via neutralizing antibody. Grafts were evaluated in vivo by ophthalmic slit-lamp biomicroscopy and anterior segment optical coherence tomography (OCT) up to 8 weeks after surgery. Additionally, whole-mount corneas were analyzed for lymphatic and blood vessels and macrophages by immunofluorescent microscopy, and draining lymph nodes were assessed for donor-derived cells by flow cytometry.
  
  
  
  Anti-Ang-2 treatment significantly suppressed LG and graft rejection. In this study, we achieved 75% suppression of LG and 80% graft survival. Our approach also inhibited donor-derived cell trafficking to draining lymph nodes and affected macrophage morphologic phenotypes in the grafted corneas. Additionally, Ang-2 blockade also reduced central corneal thickening, a parameter strongly associated with graft rejection.
  
  
  
  Ang-2 is critically involved in corneal transplant rejection and anti-Ang-2 treatment significantly improves the outcomes of corneal grafts. Moreover, we have shown that anterior segment OCT offers a new tool to monitor murine corneal grafts in vivo. This study not only reveals new mechanisms for transplant rejection, but also offers a novel strategy to treat it.
authors.affiliation: Vision Science Graduate Group, University of California, Berkeley, California, United States 2Center for Eye Disease and Development, Program in Vision Science and School of Optometry, University of California, Berkeley, California, United States 3Department of Ophthalmology, Second Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Liwei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Vision Science Graduate Group, University of California, Berkeley, California, United States 2Center for Eye Disease and Development, Program in Vision Science and School of Optometry, University of California, Berkeley, California, United States.
authors.forename: Guangyu
authors.initials: G
authors.lastname: Li
authors.affiliation: Vision Science Graduate Group, University of California, Berkeley, California, United States 2Center for Eye Disease and Development, Program in Vision Science and School of Optometry, University of California, Berkeley, California, United States.
authors.forename: Roberto
authors.initials: R
authors.lastname: Sessa
authors.affiliation: Vision Science Graduate Group, University of California, Berkeley, California, United States 2Center for Eye Disease and Development, Program in Vision Science and School of Optometry, University of California, Berkeley, California, United States.
authors.forename: Gyeong Jin
authors.initials: GJ
authors.lastname: Kang
authors.affiliation: Vision Science Graduate Group, University of California, Berkeley, California, United States 2Center for Eye Disease and Development, Program in Vision Science and School of Optometry, University of California, Berkeley, California, United States 3Department of Ophthalmology, Second Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Shi
authors.affiliation: Vision Science Graduate Group, University of California, Berkeley, California, United States 2Center for Eye Disease and Development, Program in Vision Science and School of Optometry, University of California, Berkeley, California, United States.
authors.forename: Shaokui
authors.initials: S
authors.lastname: Ge
authors.affiliation: Vision Science Graduate Group, University of California, Berkeley, California, United States 2Center for Eye Disease and Development, Program in Vision Science and School of Optometry, University of California, Berkeley, California, United States.
authors.forename: Anna Jiang
authors.initials: AJ
authors.lastname: Gong
authors.affiliation: Vision Science Graduate Group, University of California, Berkeley, California, United States 2Center for Eye Disease and Development, Program in Vision Science and School of Optometry, University of California, Berkeley, California, United States.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wen
authors.affiliation: Angiogenesis & Tumor Microenvironment Biology, Eli Lilly and Company, Indianapolis, Indiana, United States.
authors.forename: Sudhakar
authors.initials: S
authors.lastname: Chintharlapalli
authors.affiliation: Vision Science Graduate Group, University of California, Berkeley, California, United States 2Center for Eye Disease and Development, Program in Vision Science and School of Optometry, University of California, Berkeley, California, United States.
authors.forename: Lu
authors.initials: L
authors.lastname: Chen
mesh_terms: D042702:Angiopoietin-2 / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D000818:Animals; D057134:Antibodies, Neutralizing / Q000627:therapeutic use*; D003315:Cornea / Q000378:metabolism / Q000473:pathology*; D016510:Corneal Neovascularization / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D016039:Corneal Transplantation; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006085:Graft Survival / Q000187:drug effects*; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D033401:Microscopy, Acoustic; D008856:Microscopy, Fluorescence; D041623:Tomography, Optical Coherence; D014184:Transplantation, Homologous
chemical_list: D042702:Angiopoietin-2; D057134:Antibodies, Neutralizing