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 journalArticle

17 Citations (Scopus)

Abstract

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
Volume26
Issue number2
DOIs
Publication statusPublished - Feb 1 2012

Fingerprint

Reentry
Lymphatic Endothelium
Cornea
Leukocytes
Endothelial cells
Fibroblast Growth Factor 2
Endothelial Cells
Electron microscopy
Vascular Endothelial Growth Factor A
Drainage
Corneal Stroma
Lymphatic Vessels
Visualization
Genetic Predisposition to Disease
Inbred C57BL Mouse
Imaging techniques
Immunity
Electron Microscopy
Phenotype
cadherin 5

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Discontinuous LYVE-1 expression in corneal limbal lymphatics : Dual function as microvalves and immunological hot spots. / Nakao, Shintaro; Zandi, Souska; Faez, Sepideh; Kohno, Ri Ichiro; Hafezi-Moghadam, Ali.

In: FASEB Journal, Vol. 26, No. 2, 01.02.2012, p. 808-817.

Research output: Contribution to journalArticle

Nakao, Shintaro ; Zandi, Souska ; Faez, Sepideh ; Kohno, Ri Ichiro ; Hafezi-Moghadam, Ali. / Discontinuous LYVE-1 expression in corneal limbal lymphatics : Dual function as microvalves and immunological hot spots. In: FASEB Journal. 2012 ; Vol. 26, No. 2. pp. 808-817.
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