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. 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). 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.
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. 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). 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.
Authors: Don Yuen; Sammy Grimaldo; Roberto Sessa; Tatiana Ecoiffier; Tan Truong; Eric Huang; Michael Bernas; Sarah Daley; Marlys Witte; Lu Chen Journal: Invest Ophthalmol Vis Sci Date: 2014-04-29 Impact factor: 4.799
Authors: Tina Dietrich; Jasmine Onderka; Felix Bock; Friedrich E Kruse; Dörte Vossmeyer; Roland Stragies; Grit Zahn; Claus Cursiefen Journal: Am J Pathol Date: 2007-07 Impact factor: 4.307
Authors: Dongwon Choi; Eunkyung Park; Eunson Jung; Boksik Cha; Somin Lee; James Yu; Paul M Kim; Sunju Lee; Yeo Jin Hong; Chester J Koh; Chang-Won Cho; Yifan Wu; Noo Li Jeon; Alex K Wong; Laura Shin; S Ram Kumar; Ivan Bermejo-Moreno; R Sathish Srinivasan; Il-Taeg Cho; Young-Kwon Hong Journal: JCI Insight Date: 2019-03-07
Authors: Gyeong Jin Kang; Tan Truong; Eric Huang; Valerie Su; Shaokui Ge; Lu Chen Journal: Invest Ophthalmol Vis Sci Date: 2016-11-01 Impact factor: 4.799