ArticleInvestigative ophthalmology & visual science2016
Integrin Alpha 9 Blockade Suppresses Lymphatic Valve Formation and Promotes Transplant Survival.
Article in Investigative ophthalmology & visual science, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Renal denervation attenuates cardiac inflammatory responses via the afferent renal-splenic nerve axis after myocardial ischemic injury.Journal of translational medicine · 2025Article
- New targets of nascent lymphatic vessels in ocular diseases.Frontiers in physiology · 2024Review
- Lymphangiogenesis Guidance Mechanisms and Therapeutic Implications in Pathological States of the Cornea.Cells · 2023Review
- Review
- Integrin-α9β1 as a Novel Therapeutic Target for Refractory Diseases: Recent Progress and Insights.Frontiers in immunology · 2021Review
- Organogenesis and distribution of the ocular lymphatic vessels in the anterior eye.JCI insight · 2020Article
- Role of Endogenous Regulators of Hem- And Lymphangiogenesis in Corneal Transplantation.Journal of clinical medicine · 2020Review
- TGFBIp mediates lymphatic sprouting in corneal lymphangiogenesis.Journal of cellular and molecular medicine · 2019Article
- Lymphatic vessels identified in failed corneal transplants with neovascularisation.The British journal of ophthalmology · 2019Article
- Angiogenesis and lymphangiogenesis in corneal transplantation-A review.Survey of ophthalmologyReview
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Authors and funding
6 authors.
Funding
Abstract
purposeThe lymphatic pathway mediates transplant rejection. We recently reported that lymphatic vessels develop luminal valves in the cornea during lymphangiogenesis, and these valves express integrin alpha 9 (Itga-9) and play a critical role in directing lymph flow. In this study, we used an allogeneic corneal transplantation model to investigate whether Itga-9 blockade could suppress valvulogenesis after transplantation, and how this effect would influence the outcomes of the transplants.
methodsOrthotopic corneal transplantation was performed between fully mismatched C57BL/6 (donor) and BALB/c (recipient) mice. The recipients were randomized to receive subconjunctival injections of either Itga-9 blocking antibody or isotype control twice a week for 8 weeks. Corneal grafts were assessed in vivo by ophthalmic slit-lamp biomicroscopy and analyzed using Kaplan-Meier survival curves. Additionally, whole-mount full-thickness corneas were evaluated ex vivo by immunofluorescent microscopy on both lymphatic vessels and valves.
resultsAnti-Itga-9 treatment suppressed lymphatic valvulogenesis after transplantation. Our treatment did not affect lymphatic vessel formation or their nasal polarized distribution in the cornea. More importantly, Itga-9 blockade led to a significant promotion of graft survival.
conclusionsLymphatic valvulogenesis is critically involved in transplant rejection. Itga-9 targeting may offer a new and effective strategy to interfere with the immune responses and promote graft survival.
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