Role of angiopoietin-2 in corneal lymphangiogenesis

Don Yuen, Sammy Grimaldo, Roberto Sessa, Tatiana Ecoiffier, Tan Truong, Eric Huang, Michael Bernas, Sarah Daley, Marlys Witte, Lu Chen

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Purpose. Lymphatic research has progressed rapidly in recent years. Lymphatic dysfunction has been found in myriad disorders from cancer metastasis to transplant rejection; however, effective treatment for lymphatic disorders is still limited. This study investigates the role of angiopoietin-2 (Ang-2) in corneal inflammatory lymphangiogenesis (LG) in vivo and in lymphatic endothelial cell (LEC) functions in vitro. Methods. Standard suture placement model was used to study Ang-2 expression in inflamed cornea, and corneal LG and hemangiogenesis (HG) responses in Ang-2 knockout mice. Moreover, human LEC culture system was used to examine the effect of Ang-2 gene knockdown on LEC functions using small interfering RNAs (siRNAs). The effect of siRNA treatment on corneal LG was also assessed in vivo. Results. Angiopoietin-2 was expressed on lymphatic vessels and macrophages in inflamed cornea. While corneal LG response was abolished in Ang-2 knockout mice, the HG response was also significantly suppressed with disorganized patterning. Moreover, anti-Ang-2 treatment inhibited LEC proliferation and capillary tube formation in vitro and corneal LG in vivo. Conclusions. Angiopoietin-2 is critically involved in lymphatic processes in vivo and in vitro. Further investigation of the Ang-2 pathway may provide novel insights and therapeutic strategies for lymphatic-related disorders, which occur both inside and outside the eye.

Original languageEnglish (US)
Pages (from-to)3320-3327
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume55
Issue number5
DOIs
StatePublished - Apr 29 2014

Keywords

  • Ang-2
  • Corneal lymphangiogenesis
  • Knockout mice
  • Lymphatic endothelial cells
  • Small interfering RNA

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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