Corneal Lymphatic Valve Formation in Relation to Lymphangiogenesis

Truong, Thai V.; Huang, Eric C.; Yuen, Don; Chen, Lu

doi:10.1167/iovs.13-12251

Cited by 12 publications

(18 citation statements)

References 31 publications

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“…Particularly, Bazigou et al 23 examined lymphatic valve formation in Itga-9 knockout mice and reported reduced number of valves, but not lymphatic vessels, in Itga-9 homozygotes. One possible explanation for our in vivo data with the neutralizing antibody is that Itga-9 is more highly expressed on corneal lymphatic valves than vessels, 16,17 which may render the valves more sensitive to the anti-Itga-9 treatment. This warrants further investigation.…”

Section: Discussionmentioning

confidence: 96%

“…[12][13][14][15] More recently, we have reported that corneal lymphatic vessels develop luminal valves as inflammatory LG proceeds, and these valves, consisting of endothelial layers, express integrin a9b1 (Itga-9), and function to direct lymph flow in inflamed corneas. 16,17 However, the direct role of Itga-9 in corneal lymphatic valve formation and lymphatic endothelial cell (LEC) function still remain to be elucidated, which is the focus of this study. Answers to these questions are essential for developing new therapeutic strategies for lymphatic diseases.…”

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confidence: 99%

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Integrin Alpha-9 Mediates Lymphatic Valve Formation in Corneal Lymphangiogenesis

Altiok

Ecoiffier

Sessa

et al. 2015

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. We recently reported that corneal lymphatic vessels develop integrin alpha-9 (Itga-9)-positive valves during inflammatory lymphangiogenesis. The purpose of this study was to further investigate the role of Itga-9 in corneal lymphatic valve formation in vivo and lymphatic endothelial cell (LEC) functions in vitro. METHODS.Standard murine suture placement model was used to study the effect of Itga-9 blockade on lymphatic valve formation in vivo using Itga-9 neutralizing antibody. Wholemount corneas were harvested for immunofluorescent microscopic analysis. Additionally, human LEC culture system was used to examine the effect of Itga-9 gene knockdown on cell functions using small interfering RNAs (siRNAs).RESULTS. Itga-9 blockade in vivo significantly reduced the number of lymphatic valves formed in the inflamed cornea. Moreover, Itga-9 gene knockdown in human LECs suppresses cell functions of proliferation, adhesion, migration, and tube formation.CONCLUSIONS. Itga-9 is critically involved in corneal lymphatic valve formation. Further investigation of the Itga-9 pathway may provide novel strategies to treat lymphatic-related diseases occurring both inside and outside the eye.

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Section: Discussionmentioning

confidence: 96%

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confidence: 99%

Integrin Alpha-9 Mediates Lymphatic Valve Formation in Corneal Lymphangiogenesis

Altiok

Ecoiffier

Sessa

et al. 2015

Invest. Ophthalmol. Vis. Sci.

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“…7–9 Briefly, whole-mount full-thickness corneas were harvested at 8 weeks after transplantation and fixed in acetone for immunofluorescent staining. Samples were sequentially incubated with purified rabbit anti-mouse LYVE-1 (Abcam, Cambridge, MA, USA) antibody and goat anti-mouse Itga-9 antibody (R&D Systems, Minneapolis, MN, USA), which were visualized by FITC-conjugated donkey anti-rabbit and Cy3-conjugated donkey anti-goat secondary antibodies (Jackson ImmunoResearch Laboratories), respectively.…”

Section: Methodsmentioning

confidence: 99%

“…7–9 It is yet to be determined whether an intervention of the formation of these lymphatic valves, or valvulogenesis (VG), can modulate transplant survival, which is a focus of this study.…”

mentioning

confidence: 99%

“…10 Previously, we reported that this molecule is highly expressed on newly formed lymphatic valves in the cornea, 7–9 and its gene knockdown can inhibit the functions of human dermal lymphatic endothelial cells in vitro, such as proliferation, adhesion, migration, and tube formation. We demonstrated with a suture placement model that Itga-9 blockade can suppress inflammatory VG in a brief 2-week study.…”

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Integrin Alpha 9 Blockade Suppresses Lymphatic Valve Formation and Promotes Transplant Survival

Kang

Truong

Huang

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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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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Ocular Lymphatics and Lymphangiogenesis

Chen

2024

Reference Module in Neuroscience and Biobehavioral Psychology

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Corneal Lymphatic Valve Formation in Relation to Lymphangiogenesis

Abstract: This study presents new insights into corneal lymphatic valve formation and function in inflammatory LG. Further investigation on lymphatic valves may provide novel strategies to interfere with lymphatic maturation and function and to treat lymphatic-related disorders.

Cited by 12 publications

References 31 publications

Integrin Alpha-9 Mediates Lymphatic Valve Formation in Corneal Lymphangiogenesis

Integrin Alpha-9 Mediates Lymphatic Valve Formation in Corneal Lymphangiogenesis

Integrin Alpha 9 Blockade Suppresses Lymphatic Valve Formation and Promotes Transplant Survival

Ocular Lymphatics and Lymphangiogenesis

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