Spontaneous corneal hem- and lymphangiogenesis in mice with destrin-mutation depend on VEGFR3 signaling

Am J Pathol. 2005 May;166(5):1367-77. doi: 10.1016/S0002-9440(10)62355-3.


Lymphangiogenesis, the formation of new lymphatic vessels, is important for tumor metastasis and induction of immunity to peripheral antigens including organ transplants. We herein describe a novel mouse model of spontaneous, secondary lymphangiogenesis in the normally avascular cornea. corn1 mice, which suffer from a deletion in the gene encoding the cytoskeletal protein destrin, develop hemangiogenesis as well as spontaneous outgrowth of LYVE-1+++/CD31+ lymphatic vessels into the cornea starting at age 4 weeks. Corneal lymphangiogenesis is delayed in onset, is less intense, and regresses earlier compared with hemangiogenesis. Moreover, the lymphangiogenesis is preceded only by a mild recruitment of CD45+ inflammatory cells into the cornea. In contrast to mice with inflammation-induced hem- and lymphangiogenesis, corn1 mice do not develop breakdown of the blood-aqueous barrier. Finally, in this novel mouse model, a blocking anti-VEGFR3 antibody significantly inhibited not only lymph- but also hemangiogenesis. In summary, destrin deletion has differential effects on spontaneous hem- and lymphangiogenesis in the normally avascular cornea and represents a novel mouse model to study the mechanisms of lymphangiogenesis and to test the antihem- and antilymphangiogenic properties of known or new antiangiogenic agents.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actin Depolymerizing Factors
  • Animals
  • Aqueous Humor / cytology
  • Aqueous Humor / metabolism
  • Cornea / blood supply
  • Cornea / physiology*
  • Destrin
  • Eye Proteins / metabolism
  • Growth Substances / genetics
  • Leukocyte Count
  • Limbus Corneae / metabolism
  • Lymphangiogenesis / physiology*
  • Lymphatic System / metabolism
  • Mice
  • Microfilament Proteins / deficiency
  • Microfilament Proteins / genetics*
  • Mutation*
  • Neovascularization, Physiologic / physiology*
  • Protein Isoforms / metabolism
  • RNA, Messenger / metabolism
  • Signal Transduction / physiology*
  • Time Factors
  • Vascular Endothelial Growth Factor A / metabolism
  • Vascular Endothelial Growth Factor Receptor-3 / metabolism*


  • Actin Depolymerizing Factors
  • Destrin
  • Dstn protein, mouse
  • Eye Proteins
  • Growth Substances
  • Microfilament Proteins
  • Protein Isoforms
  • RNA, Messenger
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factor Receptor-3