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Angiopoietin-2 Blockade Promotes Survival of Corneal Transplants.
Zhang, Liwei; Li, Guangyu; Sessa, Roberto; Kang, Gyeong Jin; Shi, Meng; Ge, Shaokui; Gong, Anna Jiang; Wen, Ying; Chintharlapalli, Sudhakar; Chen, Lu.
Afiliação
  • Zhang L; 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
  • Li G; 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.
  • Sessa R; 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.
  • Kang GJ; 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.
  • Shi M; 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
  • Ge S; 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.
  • Gong AJ; 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.
  • Wen Y; 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.
  • Chintharlapalli S; Angiogenesis & Tumor Microenvironment Biology, Eli Lilly and Company, Indianapolis, Indiana, United States.
  • Chen L; 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.
Invest Ophthalmol Vis Sci ; 58(1): 79-86, 2017 01 01.
Article em En | MEDLINE | ID: mdl-28061513
Purpose: 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. Methods: 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. Results: 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. Conclusions: 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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transplante de Córnea / Neovascularização da Córnea / Córnea / Angiopoietina-2 / Anticorpos Neutralizantes / Sobrevivência de Enxerto Limite: Animals Idioma: En Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transplante de Córnea / Neovascularização da Córnea / Córnea / Angiopoietina-2 / Anticorpos Neutralizantes / Sobrevivência de Enxerto Limite: Animals Idioma: En Ano de publicação: 2017 Tipo de documento: Article