ArticleInvestigative ophthalmology & visual science2011
Combined blockade of VEGFR-3 and VLA-1 markedly promotes high-risk corneal transplant survival.
Article in Investigative ophthalmology & visual science, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- The Immunopathogenesis of uveitis.Frontiers in medicine · 2026Review
- Review
- CXCL10 suppression of hem- and lymph-angiogenesis in inflamed corneas through MMP13.Angiogenesis · 2017Article
- Effect of sorafenib in a murine high risk penetrating keratoplasty model.International journal of ophthalmology · 2017Article
- Angiopoietin-2 Blockade Promotes Survival of Corneal Transplants.Investigative ophthalmology & visual science · 2017Article
- Inhibition of lymphangiogenesis in vitro and in vivo by the multikinase inhibitor nintedanib.Drug design, development and therapy · 2017Article
- Integrin Alpha 9 Blockade Suppresses Lymphatic Valve Formation and Promotes Transplant Survival.Investigative ophthalmology & visual science · 2016Article
- High-risk corneal allografts: A therapeutic challenge.World journal of transplantation · 2016Review
- Intravital Imaging Reveals Dynamics of Lymphangiogenesis and Valvulogenesis.Scientific reports · 2016Article
- Integrin Alpha-9 Mediates Lymphatic Valve Formation in Corneal Lymphangiogenesis.Investigative ophthalmology & visual science · 2015Article
- Involvement of lysosomal degradation in VEGF-C-induced down-regulation of VEGFR-3.FEBS letters · 2014Article
- Soluble vascular endothelial growth factor receptor-3 suppresses allosensitization and promotes corneal allograft survival.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2014Article
- Mutation of threonine 34 in mouse podoplanin-Fc reduces CLEC-2 binding and toxicity in vivo while retaining antilymphangiogenic activity.The Journal of biological chemistry · 2014Article
- Role of angiopoietin-2 in corneal lymphangiogenesis.Investigative ophthalmology & visual science · 2014Article
- Corneal lymphatic valve formation in relation to lymphangiogenesis.Investigative ophthalmology & visual science · 2014Article
- Article
- Vascular Endothelial Growth Factor Receptor 1 morpholino increases graft survival in a murine penetrating keratoplasty model.Investigative ophthalmology & visual science · 2012Article
- Vascular endothelial growth factor-C promotes alloimmunity by amplifying antigen-presenting cell maturation and lymphangiogenesis.Investigative ophthalmology & visual science · 2012Article
- Conjunctival lymphatic response to corneal inflammation in mice.Journal of ophthalmology · 2012Article
- Understanding lymphangiogenesis in knockout models, the cornea, and ocular diseases for the development of therapeutic interventions.Survey of ophthalmologyReview
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
PURPOSE. High-risk corneal transplantation refers to grafting performed on inflamed and highly vascularized host beds. It represents a clinical dilemma because the rejection rate can be as high as 90%, irrespective of current treatment modalities. This study was conducted to investigate whether combined blockade of VEGFR-3 (vascular endothelial growth factor receptor-3) and VLA-1 (very late antigen-1) promotes high-risk transplant survival and how it correlates with corneal lymphangiogenesis and hemangiogenesis before and after transplantation. METHODS. High-risk corneal transplantation was performed between normal C57BL/6 (donor) and inflamed BALB/c (recipient) mice. The recipients were randomized to receive intraperitoneal injections of VEGFR-3 and VLA-1-neutralizing antibodies or their controls twice a week for up to 8 weeks after transplantation. Corneal grafts were evaluated by ophthalmic slit-lamp biomicroscopy and analyzed by Kaplan-Meier survival curve. Additionally, whole-mount corneas before and after transplantation were examined by immunofluorescent microscopic assays, and the correlation between lymphatic or blood vessel distribution and transplant outcome was analyzed. RESULTS. The combined blockade markedly promotes 90% survival of high-risk transplants. This strategy specifically modified host beds by selective inhibition of lymphangiogenesis but not hemangiogenesis. A strong correlation was also identified between high-risk transplant rejection and severe lymphatic invasion reaching the donor-graft border. CONCLUSIONS. These novel findings not only provide a new and potentially powerful strategy to promote high-risk transplant survival, they also confirm a critical role of high-degree lymphangiogenesis in mediating high-risk transplant rejection. Results from this study may also shed new light on our understanding and management of other lymphatic- and immune-related diseases in general.
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