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Angiopoietin-2 Blockade Promotes Survival of Corneal Transplants.
- Source :
-
Investigative ophthalmology & visual science [Invest Ophthalmol Vis Sci] 2017 Jan 01; Vol. 58 (1), pp. 79-86. - Publication Year :
- 2017
-
Abstract
- 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.<br />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.<br />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.<br />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.
- Subjects :
- Angiopoietin-2 immunology
Angiopoietin-2 metabolism
Animals
Cornea metabolism
Corneal Neovascularization immunology
Corneal Neovascularization metabolism
Disease Models, Animal
Flow Cytometry
Lymph Nodes immunology
Lymph Nodes pathology
Male
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Microscopy, Acoustic
Microscopy, Fluorescence
Tomography, Optical Coherence
Transplantation, Homologous
Angiopoietin-2 antagonists & inhibitors
Antibodies, Neutralizing therapeutic use
Cornea pathology
Corneal Neovascularization drug therapy
Corneal Transplantation
Graft Survival drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1552-5783
- Volume :
- 58
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Investigative ophthalmology & visual science
- Publication Type :
- Academic Journal
- Accession number :
- 28061513
- Full Text :
- https://doi.org/10.1167/iovs.16-20485