Discontinuous LYVE-1 expression in corneal limbal lymphatics: Dual function as microvalves and immunological hot spots

Shintaro Nakao, Souska Zandi, Sepideh Faez, Ri Ichiro Kohno, Ali Hafezi-Moghadam

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)


LYVE-1+ corneal lymphatics contribute to drainage and immunity. LYVE-1 is widely accepted as the most reliable lymphatic marker because of its continuous expression in lymphatic endothelium. LYVE-1 expression in corneal lymphatics has not been examined. In this study, we report intact CD31 + corneal lymphatic capillary endothelial cells that do not express LYVE-1. The number of LYVE-1- gaps initially increased until 8 wk of age but was significantly reduced in aged mice. C57BL/6 mice showed a notably higher number of the LYVE-1-/CD31+ lymphatic regions than BALB/c mice, which suggests a genetic predisposition for this histological feature. The LYVE-1- lymphatic gaps expressed podoplanin and VE-cadherin but not αSMA or FOXC2. Interestingly, the number of LYVE-1- gaps in FGF-2, but not VEGF-A, implanted corneas was significantly lower than in untreated corneas. Over 70% of the CD45+ leukocytes were found in the proximity of the LYVE-1- gaps. Using a novel in vivo imaging technique for visualization of leukocyte migration into and out of corneal stroma, we showed reentry of extravasated leukocytes from angiogenic vessels into newly grown corneal lymphatics. This process was inhibited by VE-cadherin blockade. To date, existence of lymphatic valves in cornea is unknown. Electron microscopy showed overlapping lymphatic endothelial ends, reminiscent of microvalves in corneal lymphatics. This work introduces a novel corneal endothelial lymphatic phenotype that lacks LYVE-1. LYVE-1 - lymphatic endothelium could serve as microvalves, supporting unidirectional flow, as well as immunological hot spots that facilitate reentry of stromal macropahges.

Original languageEnglish
Pages (from-to)808-817
Number of pages10
JournalFASEB Journal
Issue number2
Publication statusPublished - Feb 2012
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics


Dive into the research topics of 'Discontinuous LYVE-1 expression in corneal limbal lymphatics: Dual function as microvalves and immunological hot spots'. Together they form a unique fingerprint.

Cite this