Purchase this article with an account.
C. Cursiefen, L. Chen, M. Saint–Geniez, P. Hamrah, B. Pytowski, W. Streilein, R. Dana; Nonvascular VEGFR3–Expression by Corneal Epithelium Maintains Avascularity and Vision . Invest. Ophthalmol. Vis. Sci. 2006;47(13):3905.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
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. The molecular basis of corneal avascularity is poorly understood.
The mouse model of suture–induced, inflammatory corneal neovascularisation as well as several other surgical manipulations of the corneal surface (scraping, epithelial sheet transplantation etc.) were used in combination with blocking antibodies, PCR analysis, immunoblotting and confocal microscopy of immunohistochemically stained corneal flat–mounts.
We demonstrate that (i) VEGF receptor 3, normally present on lymphatic and proliferating blood vascular endothelium, is strongly expressed by corneal epithelium, and that (ii) this ectopic expression is mechanistically responsible for suppressing inflammation–driven angiogenesis (using different models of corneal neovascularization). Finally, we demonstrate that (iii) a VEGF receptor 3–IgG chimeric protein that traps VEGF receptor 3 ligands VEGF–C/–D can substitute for the antiangiogenic properties of the corneal epithelium in vivo, and that ex vivo neutralization of corneal epithelial VEGF receptor 3 with a blocking antibody impairs the anti–angiogenic properties of corneal epithelium in vivo. Ligation of corneal epithelial VEGFR3 with VEGF–C leads to increased phosphorylation of the receptor.
Nonvascular corneal epithelial expression of VEGF receptor 3 constitutes a novel antiangiogenic aspect of this receptor through which the proangiogenic functions of VEGF receptor 3 ligands (i.e. VEGF–C/–D) can be regulated. This is a potent and critical antiangiogenic mechanism contributing to corneal avascularity and vision.
This PDF is available to Subscribers Only