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PNAS 103 (30): 11405-11410

Copyright © 2006 by the National Academy of Sciences.


Nonvascular VEGF receptor 3 expression by corneal epithelium maintains avascularity and vision

Claus Cursiefen*,{dagger}, Lu Chen*, Magali Saint-Geniez*, Pedram Hamrah*, Yiping Jin*, Saadia Rashid*, Bronislaw Pytowski{ddagger}, Kris Persaud{ddagger}, Yan Wu{ddagger}, J. Wayne Streilein*,§, and Reza Dana*

*Schepens Eye Research Institute and Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, 20 Staniford Street, Boston, MA 02114; {dagger}Department of Ophthalmology, Friedrich-Alexander University Erlangen-Nürnberg, Schwabachanlage 6, 91054 Erlangen, Germany; and {ddagger}ImClone Systems, Inc., 180 Varick Street, New York, NY 10014

Edited by Judah Folkman, Harvard Medical School, Boston, MA, and approved June 9, 2006

Received for publication July 22, 2005.

Abstract: Transparency of the cornea, the window of the eye, is a prerequisite for vision. Angiogenesis into the normally avascular cornea is incompatible with good vision and, therefore, the cornea is one of the few tissues in the human body where avascularity is actively maintained. Here, we provide evidence for a critical mechanism contributing to corneal avascularity. VEGF receptor 3, normally present on lymphatic and proliferating blood vascular endothelium, is strongly constitutively expressed by corneal epithelium and is mechanistically responsible for suppressing inflammatory corneal angiogenesis.

Key Words: angiogenesis • cornea • lymphatics • inflammation

§Deceased March 15, 2004.

Author contributions: C.C., M.S.-G., J.W.S., and R.D. designed research; C.C., L.C., M.S.-G., P.H., Y.J., S.R., B.P., K.P., and Y.W. performed research; L.C., Y.J., S.R., B.P., K.P., and Y.W. contributed new reagents/analytic tools; C.C., J.W.S., and R.D. analyzed data; and C.C., J.W.S., and R.D. wrote the paper.

Conflict of interest statement: No conflicts declared.

This paper was submitted directly (Track II) to the PNAS office.

To whom correspondence should be addressed. E-mail: dana{at}

© 2006 by The National Academy of Sciences of the USA

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