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Eda Altiok, Tatiana Ecoiffier, Roberto Sessa, Don Yuen, Sammy Grimaldo, Colin Tran, David Li, Michael Rosner, Narae Lee, Toshimitsu Uede, Lu Chen; Integrin Alpha-9 Mediates Lymphatic Valve Formation in Corneal Lymphangiogenesis. Invest. Ophthalmol. Vis. Sci. 2015;56(11):6313-6319. doi: 10.1167/iovs.15-17509.
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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.
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. Whole-mount 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).
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.
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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